Chikungunya Virus

Classification

General Characteristics

Basic features

Chikungunya virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology:

• Togaviridae Togaviridae A family of RNA viruses, mainly arboviruses, consisting of two genera: alphavirus (group A arboviruses), and rubivirus. Virions are spherical, 60-70 nm in diameter, with a lipoprotein envelope tightly applied to the icosahedral nucleocapsid. Rubella Virus family
• Alphavirus Alphavirus A genus of togaviridae, also known as group a arboviruses, serologically related to each other but not to other togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. Equine Encephalitis Viruses genus
• Genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics:
  • Positive-sense, single-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
  • Size: 11.8 kb
• Properties:
  • Enveloped
  • Lipid-bilayer envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology has viral-encoded glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates, which mediate cell attachment and entry: 
    • E1 E1 An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from androstenedione directly, or from testosterone via estradiol. In humans, it is produced primarily by the cyclic ovaries, placenta, and the adipose tissue of men and postmenopausal women. Noncontraceptive Estrogen and Progestins: consists of fusion peptides, which dissociate from E2 in low pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance and facilitate the release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology of nucleocapsids into the host cytoplasm
    • E2: binds to cellular receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, resulting in receptor-mediated endocytosis Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. The Cell: Cell Membrane
  • Small, icosahedral capsid Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of capsid proteins which when assembled together form either an icosahedral or helical shape. Virology

Epidemiology

Geographic distribution:

• Frequent outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza:
  • Africa
  • Southeast Asia ASIA Spinal Cord Injuries 
• 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 virus Zika virus An arbovirus in the flavivirus genus of the family flaviviridae. Originally isolated in the zika forest of uganda it has been introduced to Asia and the americas. Zika Virus Infection and dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology):
  • A. aegypti 
  • A. albopictus

Reservoirs

• Humans
• Primates: The virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology is seen in Africa and maintained in the sylvatic cycle Cycle The type of signal that ends the inspiratory phase delivered by the ventilator Invasive Mechanical Ventilation (e.g., wild primates, monkeys, and mosquitoes).

Transmission

• Transmitted from mosquitoes to humans
• Vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections (rare)
• Blood transfusion (rare)

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 Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus or cardiovascular disease

Pathophysiology

• Chikungunya virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology 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. Skin: Structure and Functions and bloodstream via a mosquito bite.
• Viral replication occurs in the dermal fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis, then the bloodstream:
  • The virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology directly invades and replicates within the joints and muscles.
  • ↑ In proinflammatory cytokines Proinflammatory Cytokines Metabolic Syndrome 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: Anatomy (endothelial cells)
  • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification (endothelial and epithelial cells)
  • Lymphoid tissue ( lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy 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: Anatomy)
• Chronic joint disease is seen in up to 60% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and caused by:
  • Persistent viral replication
  • Continued immune response to remaining RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. 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 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
• 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 Rash Rocky Mountain Spotted Fever
• 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 Meningoencephalitis Encephalitis)

Infection of children and adults

The incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus 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 Arthralgia Pain in the joint. Rheumatic Fever and arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis:
  • Bilateral and symmetric
  • Polyarticular: commonly involves the small joints of the hands, wrists, and ankles
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are often in a flexed posture due to pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.
  • The development of chronic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis 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 Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Muscle pain Muscle Pain Ion Channel Myopathy
• Maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever (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 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

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 Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
• 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 An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and relevant exposure (i.e., travel to or living in an endemic area)
• Confirmatory tests:
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus via ELISA ELISA An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. St. Louis Encephalitis Virus or indirect fluorescent antibody (IFA):
    • IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions noted by the 5th day of symptom onset and may persist up to 3 months
    • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis noted by 2 weeks after symptom onset
  • RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) of chikungunya virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure
  • Viral culture Viral culture West Nile Virus

Additional tests

Because the symptom complexes are similar and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be coinfected with more than 1 virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology, the CDC and WHO recommend testing for chikungunya, dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus, 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 Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis
• ↑ 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 Analgesia Methods of pain relief that may be used with or in place of analgesics. Anesthesiology: History and Basic Concepts:
  • 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 An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 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 NSAIDS Primary vs Secondary Headaches and aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) until dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus 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 Rash Rocky Mountain Spotted Fever spontaneously resolves and symptoms generally improve within 1 month.

Post-acute disease

• Symptoms may persist or relapse Relapse Relapsing Fever, especially joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways.
• Analgesics such as 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 and/or NSAIDs NSAIDS Primary vs Secondary Headaches can be used.
• For severe synovitis Synovitis Inflammation of the synovial membrane. Rheumatoid Arthritis 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) ( DMARDs DMARDs 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 Methotrexate An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. Antimetabolite Chemotherapy and sulfasalazine Sulfasalazine A drug that is used in the management of inflammatory bowel diseases. Its activity is generally considered to lie in its metabolic breakdown product, 5-aminosalicylic acid released in the colon. Sulfonamides and Trimethoprim can be given.

Prevention

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

• Insect repellent Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus
• Wear protective clothing.
• Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep under a mosquito net.

Comparisons of Species

Chikungunya virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology and the equine 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 virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology belong to the Alphavirus Alphavirus A genus of togaviridae, also known as group a arboviruses, serologically related to each other but not to other togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. Equine Encephalitis Viruses genus and are major etiologies of 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 in the United States.

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 Flavivirus A genus of flaviviridae containing several subgroups and many species. Most are arboviruses transmitted by mosquitoes or ticks. The type species is yellow fever virus. Tick-borne Encephalitis Virus genus:

• Dengue Dengue An acute febrile disease transmitted by the bite of aedes mosquitoes infected with dengue virus. It is self-limiting and characterized by fever, myalgia, headache, and rash. Severe dengue is a more virulent form of dengue. Dengue Virus virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: a small, positive-sense, single-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology transmitted to humans by the bite of a female Aedes mosquito. Most infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are asymptomatic. Symptomatic individuals may progress through different stages. The febrile phase Febrile phase Dengue Virus 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 Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, retro-orbital pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, arthralgias, and maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever. 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 Critical phase Dengue Virus. Resolution of signs and symptoms occur in the convalescent phase Convalescent phase Dengue Virus. 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 Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing, or PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR). Management is supportive.  
• Zika virus Zika virus An arbovirus in the flavivirus genus of the family flaviviridae. Originally isolated in the zika forest of uganda it has been introduced to Asia and the americas. Zika Virus Infection: a positive-sense, single-stranded RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology most commonly transmitted by an A. aegypti mosquito. The virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology can also be transmitted sexually and transplacentally. Most infected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic, but some may present with low-grade fever Low-Grade Fever Erythema Infectiosum, pruritic rash Rash Rocky Mountain Spotted Fever, and 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. Congenital Zika syndrome Congenital Zika syndrome Zika Virus Infection is a transplacental, fetal infection, which manifests with ocular defects, microcephaly Microcephaly A congenital abnormality in which the cerebrum is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (desk reference for neuroscience, 2nd ed. ). Fetal Alcohol Spectrum Disorder, spasticity Spasticity Spinal Disk Herniation, 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 RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) or serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. Treatment is mostly supportive. Prevention includes control of the mosquito population with insect repellent Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus, and protective clothing. 

Conditions presenting as chronic arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis:

• Seronegative rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: inflammatory arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis in 3 or more joints, which lasts for > 6 weeks. Rheumatoid factor Rheumatoid factor Antibodies found in adult rheumatoid arthritis patients that are directed against gamma-chain immunoglobulins. Autoimmune Hepatitis and anti-cyclic citrullinated peptide tests are negative and could present similarly to chikungunya infection. Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and history (including travel) distinguish seronegative rheumatoid arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis from chikungunya infection.
• Reactive arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis: arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis occurring concomitantly with or after an extraarticular infection. Characteristics include asymmetric oligoarthritis Oligoarthritis Ankylosing Spondylitis (often involving the lower extremities), enthesitis Enthesitis Ankylosing Spondylitis, back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and dactylitis Dactylitis Ankylosing Spondylitis. Diagnosis is made by history (GI or urinary infection is often noted) and ruling out other arthritis Arthritis Acute or chronic inflammation of joints. Osteoarthritis etiologies with laboratory work-up and imaging.