Chikungunya Virus

Chikungunya virus belongs to the Alphavirus genus and causes a viral infection characterized by fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever and joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. The arthropod-borne (arbovirus) virus is transmitted by mosquitoes (commonly Aedes albopictus and Aedes aegypti). Symptoms usually appear within 1 week of infection. Additional manifestations of chikungunya virus may include muscle pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, headache, maculopapular rash, and lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. Most infected individuals recover, but chronic arthritis may develop. Treatment is aimed at relieving symptoms. The disease is prevented by mosquito avoidance, use of insect repellent, and protective clothing.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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Classification

Rna viruses flowchart classification

RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by either DNA DNA The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival. DNA Types and Structure or RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure genome viruses can be further characterized by either a single- or double-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure. “Enveloped” viruses are covered by a thin coat of cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane (usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses. Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly employed as messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure (mRNA), which is translated into proteins. “Negative-sense,” single-stranded viruses employ RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase, a viral enzyme, to transcribe their genome into messenger RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Basic features

Chikungunya virus:

  • Togaviridae family
  • Alphavirus genus
  • Genome:
    • Positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure
    • Size: 11.8 kb
  • Properties:
    • Enveloped
    • Lipid-bilayer envelope has viral-encoded glycoproteins, which mediate cell attachment and entry: 
      • E1: consists of fusion peptides, which dissociate from E2 in low pH and facilitate the release of nucleocapsids into the host cytoplasm
      • E2: binds to cellular receptors, resulting in receptor-mediated endocytosis
    • Small, icosahedral capsid

Epidemiology

Geographic distribution:

  • Frequent outbreaks:
    • Africa
    • Southeast Asia 
  • Indian subcontinent
  • South America and islands of the Caribbean
  • United States:
    • Cases reported from travelers to the above areas
    • Local transmission noted in Florida, Puerto Rico, and the United States Virgin Islands

Pathogenesis

Vectors

  • Mosquitoes of the Aedes genus
  • Major vectors (also transmit Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection virus and dengue virus Dengue Virus Dengue virus (DENV) is a small, positive-sense, single-stranded RNA virus of the genus Flavivirus. The infection can be transmitted to humans by the bite of female Aedes mosquitoes. The majority of infections are asymptomatic. Symptomatic individuals may progress through 3 stages of the disease, with severe manifestations occurring in those with previous infections. Dengue Virus):
    • A. aegypti 
    • A. albopictus

Reservoirs

  • Humans
  • Primates: The virus is seen in Africa and maintained in the sylvatic cycle (e.g., wild primates, monkeys, and mosquitoes).

Transmission

  • Transmitted from mosquitoes to humans
  • Vertical transmission (rare)
  • Blood transfusion (rare)
Life cycle of chikungunya virus

The life cycle of the chikungunya virus in Africa showing the interconnection between the sylvatic cycle, involving primates and mosquitoes, and the urban cycle, involving humans and mosquitoes.

Image: “Life cycle of Chikungunya virus” by Michelle M Thiboutot et al. License: CC BY 4.0

Host risk factors

  • Proximity to mosquito breeding sites
  • Severe disease can occur in:
    • Newborns 
    • Adults ≥ 65 years of age
    • Individuals with underlying conditions such as diabetes or cardiovascular disease

Pathophysiology

  • Chikungunya virus is introduced to the human skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and bloodstream via a mosquito bite.
  • Viral replication occurs in the dermal fibroblasts, then the bloodstream:
    • The virus directly invades and replicates within the joints and muscles.
    • ↑ In proinflammatory cytokines and inflammatory cells
  • Dissemination to and invasion of other organs may occur:
    • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver (endothelial cells)
    • Brain (endothelial and epithelial cells)
    • Lymphoid tissue (lymph nodes and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen)
  • Chronic joint disease is seen in up to 60% of patients and caused by:
    • Persistent viral replication
    • Continued immune response to remaining RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure 
    • Autoimmunity Autoimmunity Autoimmunity is a pathologic immune response toward self-antigens, resulting from a combination of factors: immunologic, genetic, and environmental. The immune system is equipped with self-tolerance, allowing immune cells such as T cells and B cells to recognize self-antigens and to not mount a reaction against them. Defects in this mechanism, along with environmental triggers (such as infections) and genetic susceptibility factors (most notable of which are the HLA genes) can lead to autoimmune diseases. Autoimmunity

Clinical Presentation

Neonatal infection

Infection of newborns is seen within 1 week of delivery. Signs and symptoms include:

  • Fever
  • Poor feeding
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Rash
  • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia
  • Neurologic disease (meningoencephalitis)

Infection of children and adults

The incubation period is 3–7 days. Symptoms of chikungunya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever appear within 1 week of infection and include:

  • High-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
  • Debilitating arthralgia and arthritis:
    • Bilateral and symmetric
    • Polyarticular: commonly involves the small joints of the hands, wrists, and ankles
    • Patients are often in a flexed posture due to pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain.
    • The development of chronic arthritis increases in those ≥ 45 years of age and/or with preexisting osteoarthritis Osteoarthritis Osteoarthritis (OA) is the most common form of arthritis, and is due to cartilage destruction and changes of the subchondral bone. The risk of developing this disorder increases with age, obesity, and repetitive joint use or trauma. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Osteoarthritis.
  • Headache
  • Muscle pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
  • Maculopapular rash (extremities and trunk)
  • Conjunctivitis Conjunctivitis Conjunctivitis is a common inflammation of the bulbar and/or palpebral conjunctiva. It can be classified into infectious (mostly viral) and noninfectious conjunctivitis, which includes allergic causes. Patients commonly present with red eyes, increased tearing, burning, foreign body sensation, and photophobia. Conjunctivitis
  • Lymphadenopathy

Severe symptoms may occur in those with risk factors:

  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
  • Myocarditis Myocarditis Myocarditis is an inflammatory disease of the myocardium, which may occur alone or in association with a systemic process. There are numerous etiologies of myocarditis, but all lead to inflammation and myocyte injury, most often leading to signs and symptoms of heart failure. Myocarditis
  • Hepatitis
  • Renal failure
  • Hemorrhage

Diagnosis

Diagnostics

  • Clinical history: fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, and relevant exposure (i.e., travel to or living in an endemic area)
  • Confirmatory tests:
    • Serology via ELISA or indirect fluorescent antibody (IFA):
      • IgM noted by the 5th day of symptom onset and may persist up to 3 months
      • IgG noted by 2 weeks after symptom onset
    • RT-PCR of chikungunya virus RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure
    • Viral culture

Additional tests

Because the symptom complexes are similar and patients may be coinfected with more than 1 virus, the CDC and WHO recommend testing for chikungunya, dengue, and Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection viruses in patients presenting with suspicious symptoms.

CBC:

  • Lymphopenia
  • Thrombocytopenia Thrombocytopenia Thrombocytopenia occurs when the platelet count is < 150,000 per microliter. The normal range for platelets is usually 150,000-450,000/µL of whole blood. Thrombocytopenia can be a result of decreased production, increased destruction, or splenic sequestration of platelets. Patients are often asymptomatic until platelet counts are < 50,000/µL. Thrombocytopenia

Other findings:

  • ↑ Hepatic transaminases
  • ↑ Creatinine

Management

Acute disease

Treatment of chikungunya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is symptomatic:

  • Analgesia:
    • Acetaminophen Acetaminophen Acetaminophen is an over-the-counter nonopioid analgesic and antipyretic medication and the most commonly used analgesic worldwide. Despite the widespread use of acetaminophen, its mechanism of action is not entirely understood. Acetaminophen for pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain and fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
    • Avoid NSAIDs and aspirin until dengue fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever is ruled out (due to bleeding risk).
  • Hydration

Rash spontaneously resolves and symptoms generally improve within 1 month.

Post-acute disease

  • Symptoms may persist or relapse, especially joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain.
  • Analgesics such as acetaminophen and/or NSAIDs can be used.
  • For severe synovitis and continued elevation of inflammatory markers, a short course of glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids can be given.
  • For symptoms ≥ 3 months, disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs Disease-modifying antirheumatic drugs are antiinflammatory medications used to manage rheumatoid arthritis. The medications slow, but do not cure, the progression of the disease. The medications are classified as either synthetic or biologic agents and each has unique mechanisms of action and side effects. Disease-modifying Antirheumatic Drugs (DMARDs) such as methotrexate and sulfasalazine can be given.

Prevention

Avoid mosquito breeding areas by environment control (i.e., no standing water in containers) and use personal protection:

  • Insect repellent
  • Wear protective clothing.
  • Sleep Sleep Sleep is a reversible phase of diminished responsiveness, motor activity, and metabolism. This process is a complex and dynamic phenomenon, occurring in 4-5 cycles a night, and generally divided into non-rapid eye movement (NREM) sleep and REM sleep stages. Physiology of Sleep under a mosquito net.

Comparisons of Species

Chikungunya virus and the equine encephalitis virus belong to the Alphavirus genus and are major etiologies of encephalitis in the United States.

Table: Comparison of chikungunya virus and equine encephalitis virus
Organism Chikungunya virus Equine encephalitis virus
Family Togaviridae
Genus Alphavirus
Characteristics
  • Enveloped, icosahedral capsid
  • Positive sense
  • ssRNA
Transmission Mosquito
Clinical
  • Fever
  • Headache
  • Arthritis
  • Rash
  • Fever
  • Headache
  • Nausea/vomiting
  • Severe: encephalitis
Diagnosis
  • Serology
  • RT-PCR
Management
  • Symptomatic
  • Control of joint pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain
Supportive
Prevention
  • Mosquito avoidance
  • Insect repellent
  • Protective clothing
  • Mosquito net

Differential Diagnosis

Conditions mimicking acute chikungunya fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, have a similar symptom complex, and belong to the Flaviridae family and Flavivirus genus:

  • Dengue Dengue Dengue is an infection caused by the Dengue virus (DENV), a small, positive-sense, single-stranded RNA virus of the genus Flavivirus. The majority of infections are asymptomatic. Symptomatic individuals may progress through 3 stages of the disease, with severe manifestations occurring in those with previous infections. Dengue Virus virus: a small, positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus transmitted to humans by the bite of a female Aedes mosquito. Most infections are asymptomatic. Symptomatic individuals may progress through different stages. The febrile phase includes fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache, retro-orbital pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, myalgias, arthralgias, and maculopapular rash. More severe manifestations of capillary leakage, hemorrhage, and shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock may occur in the critical phase. Resolution of signs and symptoms occur in the convalescent phase. Diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests include serology, antigen testing, or PCR. Management is supportive.  
  • Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection virus: a positive-sense, single-stranded RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure virus most commonly transmitted by an A. aegypti mosquito. The virus can also be transmitted sexually and transplacentally. Most infected patients are asymptomatic, but some may present with low-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, pruritic rash, and conjunctivitis. Congenital Zika Zika Zika virus belongs to the genus Flavivirus and is primarily transmitted by Aedes aegypti mosquitoes, but can also be transmitted sexually and transplacentally. Although most infected patients are asymptomatic, some may present with low-grade fever, pruritic rash, and conjunctivitis. Zika Virus Infection syndrome is a transplacental, fetal infection, which manifests with ocular defects, microcephaly, spasticity, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. The diagnosis is made either by RT-PCR or serology. Treatment is mostly supportive. Prevention includes control of the mosquito population with insect repellent, and protective clothing. 

Conditions presenting as chronic arthritis:

  • Seronegative rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis: inflammatory arthritis in 3 or more joints, which lasts for > 6 weeks. Rheumatoid factor and anti-cyclic citrullinated peptide tests are negative and could present similarly to chikungunya infection. Serology and history (including travel) distinguish seronegative rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis (RA) is a symmetric, inflammatory polyarthritis and chronic, progressive, autoimmune disorder. Presentation occurs most commonly in middle-aged women with joint swelling, pain, and morning stiffness (often in the hands). Rheumatoid Arthritis from chikungunya infection.
  • Reactive arthritis Reactive arthritis Reactive arthritis is a seronegative autoimmune spondyloarthropathy that occurs in response to a previous gastrointestinal (GI) or genitourinary (GU) infection. The disease manifests as asymmetric oligoarthritis (particularly of large joints in the lower extremities), enthesopathy, dactylitis, and/or sacroiliitis. Reactive Arthritis: arthritis occurring concomitantly with or after an extraarticular infection. Characteristics include asymmetric oligoarthritis (often involving the lower extremities), enthesitis, back pain Back pain Back pain is a common complaint among the general population and is mostly self-limiting. Back pain can be classified as acute, subacute, or chronic depending on the duration of symptoms. The wide variety of potential etiologies include degenerative, mechanical, malignant, infectious, rheumatologic, and extraspinal causes. Back Pain, and dactylitis. Diagnosis is made by history (GI or urinary infection is often noted) and ruling out other arthritis etiologies with laboratory work-up and imaging.

References:

  1. Centers for Disease Control and Prevention. (2019). Chikungunya virus. https://www.cdc.gov/chikungunya/
  2. Gibney, K.B., Fischer, M., Prince, H.E., et al. (2011). Chikungunya fever in the United States: a fifteen-year review of cases. Clin Infect Dis. 52(5):e121–6. http://reference.medscape.com/medline/abstract/21242326
  3. Miner, J., Lenschow, D., Wilson, M. (2021). Chikungunya fever: treatment and prevention. UpToDate. Retrieved May 22, 2021, from https://www.uptodate.com/contents/chikungunya-fever-treatment-and-prevention
  4. Natesan, S., Chandrasekar, P. (2019). Chikungunya virus. Medscape. Retrieved May 22, 2021, from https://emedicine.medscape.com/article/2225687-overview
  5. Staples, J.E., Breiman, R.F., Powers, A.M. (2009). Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis. 49(6):942–8. http://reference.medscape.com/medline/abstract/19663604
  6. Schwartz, O., Albert, M. (2010). Biology and pathogenesis of chikungunya virus. Nat Rev Microbiol 8, 491–500. https://doi.org/10.1038/nrmicro2368
  7. Thiboutot, M.M., et al. (2010). Chikungunya: A Potentially Emerging Epidemic? PLoS Negl Trop Dis 4(4): e623. https://doi.org/10.1371/journal.pntd.0000623
  8. Wilson, M., Lenschow, D., Miner, J. (2020). Chikungunya fever: Epidemiology, clinical manifestations and diagnosis. UpToDate. Retrieved May 22, 2021, from https://www.uptodate.com/contents/chikungunya-fever-epidemiology-clinical-manifestations-and-diagnosis

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