Bunyavirales

Classification

Characteristics

Basic features

• Taxonomy:
  • Order: Bunyavirales
  • Family: Bunyaviridae
  • 5 genera:
    • Hantavirus/Orthohantavirus (includes Sin Nombre 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)
    • Orthobunyavirus (includes La Crosse 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)
    • Phlebovirus (includes Rift Valley 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 (RVF) 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, sandfly Sandfly Leishmania/Leishmaniasis/Phlebotomus 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 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)
    • Nairovirus (includes Crimean-Congo hemorrhagic 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)
    • Tospovirus (infects only plants Plants Cell Types: Eukaryotic versus Prokaryotic)
• Bunyaviruses:
  • Enveloped: an 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 with 2 glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates
  • Spherical, 80–120 nm in diameter
  • 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:
    • Single-stranded negative-sense 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
    • Triple segmented
    • Presence of helical Helical Computed tomography where there is continuous x-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures. Computed Tomography (CT) 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
    • Contains RNA-dependent 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 polymerase
  • Primarily arthropod-borne or rodent-borne 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:
    • Hantavirus (rodents)
    • Orthobunyavirus (mosquitoes)
    • Nairovirus ( ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever)
    • Phlebovirus: sandfly Sandfly Leishmania/Leishmaniasis 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 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 (sandflies)
    • Phlebovirus: RVF 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 (mosquitoes)
  • Associated diseases:
    • Hemorrhagic fevers (i.e., Hantavirus, Crimean-Congo hemorrhagic 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)
    • Mosquito-borne 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 (i.e., California 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 group, which includes La Crosse 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)

Hantavirus

Etiology and epidemiology

• Genus: Hantavirus
• > 20 species (about 11 known to cause disease in humans) including:
  • Sin Nombre 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:
    • Etiology of the 1993 “Four Corners” outbreak in the southwestern US
    • Among the etiologies of hantavirus pulmonary syndrome (HPS)/hantavirus cardiopulmonary syndrome (HCPS), and a severe and potentially fatal respiratory illness
  • Seoul, Dobrava, and Puumala 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: among the etiologic agents of hemorrhagic 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 with renal syndrome (HFRS)
• Epidemiology:
  • China has the highest annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of hantavirus-related diseases.
  • 728 cases reported in the US in 2017 (most commonly found in the western and southwestern states)
  • 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 in the US are sporadic Sporadic Selective IgA Deficiency.

Pathophysiology

• Primary reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: rodents (deer mice in the US)
• Transmission:
  • Aerosol route/inhalation (exposure to feces, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy, or urine of infected mice)
  • Rodent bite
  • Direct contact (via nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose and Nasal Cavity: Anatomy or mouth) with materials contaminated with rodent droppings, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy, or urine
  • Ingestion of rodent droppings, saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy, or urine
• Major syndromes/disease processes:
  • HPS
    • Viral antigens penetrate the endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology, leading to immunologic response → ↑ capillary permeability → pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema 
    • More fatal of the 2 hantavirus syndromes
    • Caused mainly by hantavirus species in the Americas, and generally occurs in the fall in the US
  • HFRS
    • Azotemia Azotemia A biochemical abnormality referring to an elevation of blood urea nitrogen and creatinine. Azotemia can be produced by kidney diseases or other extrarenal disorders. When azotemia becomes associated with a constellation of clinical signs, it is termed uremia. Acute Kidney Injury secondary to vascular endothelial injury (capillary leak and loss of fluids)
    • Cytokine-induced tubular and interstitial damage → tubulointerstitial nephritis
    • More common of the 2 hantavirus syndromes
    • Caused mainly by hantavirus species in Asia ASIA Spinal Cord Injuries and Europe

Clinical presentation

• HPS/HCPS:
  • Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 1–3 weeks
  • Prodromal phase (up to 5 days):
    • 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
    • Muscle aches
    • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia/ diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
  • Cardiopulmonary phase (2–7 days):
    • Cough
    • Dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea: can progress to hypoxia Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage and respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure requiring mechanical ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
    • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation
    • Findings: tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Convalescent phase Convalescent phase Dengue Virus:
    • Significant diuresis
    • Resolution of symptoms
• HFRS:
  • Varies depending on species (i.e., Hantaan 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 in Asia ASIA Spinal Cord Injuries causes more severe disease)
  • Manifestations 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
    • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension (can lead to 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)
    • Hemorrhage
    • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury (↓ GFR GFR The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests, oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation, proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, and hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma)

Diagnosis and management

• Confirmatory tests:
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus (i.e., 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), where acute infection is detected as:
    • Specific anti-hantavirus 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 (usually the nucleocapsid or N antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination)
    • A 4-fold rise in anti-hantavirus 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 titers
  • 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) using plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products, blood cells, or tissues
• Additional laboratory tests:
  • CBC: leukocytosis Leukocytosis A transient increase in the number of leukocytes in a body fluid. West Nile Virus, 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
  • Hepatic panel: transaminitis Transaminitis Tick-borne Encephalitis Virus, ↓ albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests
  • HFRS: abnormal BUN/creatinine, proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children, or hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma
  • ↑ CRP
• Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:
  • HPS:
    • Interstitial 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 (in most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship after 48 hours) 
    • Perihilar haziness without cardiomegaly Cardiomegaly Enlargement of the heart, usually indicated by a cardiothoracic ratio above 0. 50. Heart enlargement may involve the right, the left, or both heart ventricles or heart atria. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (heart failure) or several forms of cardiomyopathies. Ebstein’s Anomaly
  • HFRS:
    • Can show abnormal chest radiography
    • Interstitial infiltrates, effusion, atelectasis Atelectasis Atelectasis is the partial or complete collapse of a part of the lung. Atelectasis is almost always a secondary phenomenon from conditions causing bronchial obstruction, external compression, surfactant deficiency, or scarring. Atelectasis
• Management:
  • Supportive measures:
    • Cardiorespiratory support
    • Fluid balance
    • Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis as indicated
  • Prevention: rodent control, avoiding rodent contact, and appropriate clean-up of nesting sites
  • No vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination available
• Mortality Mortality All deaths reported in a given population. Measures of Health Status:
  • HPS: up to 50% overall
  • HFRS: 5%–10%

Crimean-Congo Hemorrhagic Fever Virus

Etiology and epidemiology

• Genus: Nairovirus
• Crimean-Congo hemorrhagic 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 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
• Associated disease: Crimean-Congo hemorrhagic 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
  • 1st characterized in Crimea in 1944 (Crimean 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)
  • It was later recognized in 1956 as the cause of illness in Congo, resulting in the disease’s current name
• Epidemiology: 
  • Endemic areas:
    • Africa (primarily central)
    • Eastern Europe (particularly in the former Soviet Union) and Southern Europe
    • Mediterranean
    • Middle East
    • Northwestern China
    • Central Asia ASIA Spinal Cord Injuries
    • Indian subcontinent
  • Risk of exposure:
    • Animal herders
    • Livestock workers
    • Slaughterhouse workers

Pathophysiology

• Vector and reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: Ixodid ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever (genus: Hyalomma) can transmit 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 to progeny.
• Amplifying hosts: wild and domestic animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic, such as cattle, goats, sheep 
• Transmission:
  • Tick bites
  • Direct contact with bodily fluids of infected livestock or humans
  • Documented transmission via improperly sterilized medical equipment, needle-stick injuries, and contaminated medical supplies in hospitals
  • Vertical (mother-to-child) transmission
• Disease process:
  • 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 replicates at the site of inoculation within epithelial cells, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions → viremia Viremia The presence of viruses in the blood. Erythema Infectiosum
  • Endothelial cells are targeted by 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, triggering the release of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response and chemokines Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: c; cc; and cxc; according to variations in a shared cysteine motif. Adaptive Cell-mediated Immunity and leading to:
    • Increased vascular permeability
    • Deregulated platelet aggregation Aggregation The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin; collagen) and is part of the mechanism leading to the formation of a thrombus. Coagulation Studies → stimulated coagulation cascade Coagulation cascade The coagulation cascade is a series of reactions that ultimately generates a strong, cross-linked fibrin clot. Hemostasis (procoagulant state)
    • Clotting factors eventually become deficient → hemorrhage

Clinical presentation

• Sudden onset of flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis:
  • 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
  • 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
  • Back pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and arthralgias
  • Abdominal pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics/ vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Facial flushing
  • Injected conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy
  • Petechiae Petechiae Primary Skin Lesions on the palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy
• Symptoms last up to 7 days:
  • Most often followed by recovery
  • Can progress to severe disease with hemorrhage ( ecchymosis Ecchymosis Extravasation of blood into the skin, resulting in a nonelevated, rounded or irregular, blue or purplish patch, larger than a petechia. Orbital Fractures, epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis, gum bleeding, hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma, melena Melena The black, tarry, foul-smelling feces that contain degraded blood. Gastrointestinal Bleeding, heavy menstrual bleeding Heavy menstrual bleeding Excessive menstrual blood loss (objectively defined as > 80 mL blood loss/cycle). Can be based on heavy flow, as determined by the patient Abnormal Uterine Bleeding)
  • Exaggerated proinflammatory cytokine response (“cytokine storm”) leads to hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, 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, and multiorgan failure.
• Fatality rates in hospitalized patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship range from 9%–50%.

Diagnosis and management

• 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:
  • Diagnosis is based on physical findings and history of risk exposure.
  • 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)
  • Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus (detection of specific immunoglobulins Immunoglobulins Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions 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 and 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 using 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)
• Additional laboratory tests:
  • CBC: 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, leukopenia
  • Hepatic panel: transaminitis Transaminitis Tick-borne Encephalitis Virus, hyperbilirubinemia Hyperbilirubinemia A condition characterized by an abnormal increase of bilirubin in the blood, which may result in jaundice. Bilirubin, a breakdown product of heme, is normally excreted in the bile or further catabolized before excretion in the urine. Jaundice
  • ↑ PT/INR
  • In disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation: ↑ fibrin-degradation products, ↓ fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis
• Treatment
  • Supportive:
    • Cardiorespiratory support
    • Fluid balance
    • Blood-product replacement
  • Ribavirin Ribavirin A nucleoside antimetabolite antiviral agent that blocks nucleic acid synthesis and is used against both RNA and DNA viruses. Antivirals for Hepatitis C may offer some benefit.
  • No available vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination
• Prevention:
  • Avoiding contact with blood and body fluids of infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic
  • Wearing insect repellants and protective clothing
  • Isolation of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Using PPE

Rift Valley Fever Virus

Etiology and epidemiology

• Genus: Phlebovirus
• RVF 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 
• Associated disease: RVF (viral hemorrhagic 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)
• Epidemiology:
  • Endemic areas:
    • East Africa
    • Sub-Saharan Africa
    • Madagascar
  • Commonly affects livestock, but humans are infected secondarily

Pathophysiology

• Vector:
  • Mosquitoes: Females can transmit 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 to their eggs.
    • Aedes mosquito (primary vector)
    • Culex mosquito
  • Infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic
• Transmission:
  • Mosquito bites
  • Contact with blood or body fluids of infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic 
• Host risk factors
  • Living in rural areas
  • Sleeping outdoors at night
  • Herdsmen/farmers
  • Veterinarians
  • Butchers/slaughterhouse workers

Clinical presentation

• RVF infection can cause either mild or severe illnesses in humans.
  • Mild illness:
    • 90% of cases
    • Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have either a flu-like illness or no symptoms.
    • Recovery in 2 days to 1 week
  • Severe illness:
    • 8%–10% of cases
    • Eye disease: retinitis, lesions affecting the macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy (50% will have permanent blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity)
    • Hemorrhagic 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 (1% of cases): bleeding, 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 impairment, hematemesis Hematemesis Vomiting of blood that is either fresh bright red, or older ‘coffee-ground’ in character. It generally indicates bleeding of the upper gastrointestinal tract. Mallory-Weiss Syndrome (Mallory-Weiss Tear) (carries a 50% mortality rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status)
    • 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 (1% of cases): headaches, coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma, 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 (can lead to permanent neurological deficits)

Diagnosis and management

• 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)
• Viral isolation in cell culture
• Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus ( 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 antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against the RVF 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)
• Management
  • 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 self-limiting Self-Limiting Meningitis in Children.
  • Supportive care
  • No FDA-approved treatments 
• Prevention
  • No vaccines exist for prevention.
  • Avoid contact with the blood and body fluids of infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic.
  • Mosquito avoidance:
    • Insect repellents
    • Mosquito nets
    • Protective clothing

La Crosse Virus

Etiology and epidemiology

• Genus: Orthobunyavirus
• La Crosse 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 pathogenic 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 in the California 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 serogroup
• Associated disease: La Crosse 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 (mosquito-borne arboviral disease) 
• Epidemiology:
  • La Crosse 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 common arbovirus causing CNS 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 in children (North America)
  • Approximately 75% of cases in the pediatric population
  • In the US:
    • 30–120 cases of neuroinvasive diseases reported annually 
    • Most cases are reported in the summertime with a peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency between July and September.
    • Areas most affected: upper midwestern, mid-Atlantic, and southeastern states

Pathophysiology

• Vector: the eastern tree hole mosquito, Aedes triseriatus
• Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli: A. triseriatus ( 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 passed from a female mosquito to the eggs)
• Hosts: Cycles of infection occur between mosquitoes and hosts (humans, squirrels, chipmunks, and other small mammals).
• Transmission: mosquito bite
• Pathophysiology
  • 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 transmitted subcutaneously by a feeding mosquito.
  • Viral replication begins in the muscle adjacent to the site of penetration Penetration X-rays, eventually followed by viremia Viremia The presence of viruses in the blood. Erythema Infectiosum.
  • Dissemination to the reticuloendothelial system ( lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs nodes, 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, 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) occurs, and neuroinvasion may follow.

Clinical presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus: 3–7 days
• Many infected individuals are asymptomatic or present with a mild flu-like illness:
  • 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
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia
• Few infected individuals may develop severe neuroinvasive disease Neuroinvasive disease West Nile Virus (most often children < 16 years of age):
  • 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
  • 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
  • Aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
  • Paralysis 
  • Coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma
  • Fatalities are rare.

Diagnosis and management

• Suspect 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 typical symptoms in an endemic area.
• 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:
  • 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 and neutralizing antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions to 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 in serum or CSF using 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 
  • A 4-fold increase in antibody titer 
  • Determination of viral antigens or genomic sequences in tissue, blood, or CSF
• Additional tests:
  • 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 CT scan is normal.
  • EEG EEG Seizures abnormalities are common.
• Treatment
  • Supportive
  • Usually self-limiting Self-Limiting Meningitis in Children
  • No effective antiviral Antiviral Antivirals for Hepatitis B drugs
  • No vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination available
• Prevention
  • Mosquito avoidance:
    • Insect repellent Insect repellent Substances causing insects to turn away from them or reject them as food. St. Louis Encephalitis Virus 
    • Protective clothing
    • Avoid mosquito-infested areas

Comparison of Species

Differential Diagnosis

• Saint Louis 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: a member of the genus, 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, and the cause of St. Louis encephalitis St. Louis Encephalitis A viral encephalitis caused by the St. Louis encephalitis virus, a flavivirus. It is transmitted to humans and other vertebrates primarily by mosquitoes of the genus culex. The primary animal vectors are wild birds and the disorder is endemic to the midWestern and southeastern United States. Infections may be limited to an influenza-like illness or present as an aseptic meningitis or encephalitis. Clinical manifestations of the encephalitic presentation may include seizures, lethargy, myoclonus, focal neurologic signs, coma, and death. St. Louis Encephalitis Virus. Saint Louis 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 is a small, enveloped, positive-sense ssRNA Positive-sense ssRNA Hepatitis C 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 transmitted by Culex mosquito species. 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 have varied presentations with flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis, aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, 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, or meningoencephalitis Meningoencephalitis Encephalitis. The diagnosis is confirmed with serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. There are no effective antiviral Antiviral Antivirals for Hepatitis B drugs; thus, the management is supportive. Prevention is aimed at local mosquito control and personal protection using insect repellents and protective clothing.
• Yellow fever Yellow Fever An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera aedes and haemagogus. The severe form is characterized by fever, hemolytic jaundice, and renal damage. Yellow Fever Virus: a disease caused by the yellow fever Yellow Fever An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera aedes and haemagogus. The severe form is characterized by fever, hemolytic jaundice, and renal damage. Yellow Fever 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 single-stranded, positive-sense 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 of the genus, 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. Humans and primates serve as reservoirs, and transmission occurs from the bite of an infected female mosquito. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with 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 flu-like symptoms Flu-Like Symptoms Babesia/Babesiosis in most cases. Severe disease can cause multiorgan dysfunction resulting in jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice, renal dysfunction, hemorrhage, 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, and potential death. The diagnosis can be confirmed with serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and 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). There are no antiviral Antiviral Antivirals for Hepatitis B drugs available to treat yellow fever Yellow Fever An acute infectious disease primarily of the tropics, caused by a virus and transmitted to man by mosquitoes of the genera aedes and haemagogus. The severe form is characterized by fever, hemolytic jaundice, and renal damage. Yellow Fever Virus; thus, the management is supportive. Prevention includes mosquito avoidance and vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination.
• Tick-borne encephalitis virus Tick-borne Encephalitis Virus Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus ( TBEV TBEV Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus): 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 of the genus, 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, causing 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. Transmission primarily occurs via Ixodes ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever, and 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 common in Europe, Russia, and Asia ASIA Spinal Cord Injuries. Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic; however, symptomatic individuals may experience a biphasic illness Biphasic illness Lymphocytic Choriomeningitis Virus. After recovering from nonspecific symptoms, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can develop neurologic manifestations such as meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, 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, or meningoencephalitis Meningoencephalitis Encephalitis. Serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus 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) can confirm the diagnosis. There are no effective antiviral Antiviral Antivirals for Hepatitis B drugs to treat TBEV TBEV Tick-borne encephalitis virus (TBEV) is a positive-sense, single-stranded RNA virus of the genus Flavivirus. Transmission occurs primarily via Ixodes ticks found in Europe, the former Soviet Union, and Asia. The virus causes tick-borne encephalitis. Most patients are asymptomatic; however, symptomatic individuals may experience a biphasic illness. Tick-borne Encephalitis Virus 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. Management is supportive.
• 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: is a small, positive-sense, ssRNA 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 of the genus, 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. Transmission is via the bite of female Aedes mosquitoes. 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 go through 3 stages, with severe manifestations occurring in those with previous 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. 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 and 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 and arthralgias (“breakbone” pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways), and maculopapular Maculopapular Dermatologic Examination rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes. The critical phase Critical phase Dengue Virus includes 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. There is symptom resolution in the convalescent phase Convalescent phase Dengue Virus. Diagnosis is made based on the clinical findings, 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.