Classification

General Characteristics

Basic features

• Enveloped
• Spherical
• Medium-sized agent, measuring 70–150 nm in diameter
• 2 viral surface glycoproteins on envelope: G1 and G2
• 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: Overview genome:
  • Encapsulated by a helical nucleocapsid
  • Segmented single-stranded, negative-sense RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure, made of:
    • Large (L) fragment: encodes the RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure-dependent RNA RNA Ribonucleic acid (RNA), like deoxyribonucleic acid (DNA), is a polymer of nucleotides that is essential to cellular protein synthesis. Unlike DNA, RNA is a single-stranded structure containing the sugar moiety ribose (instead of deoxyribose) and the base uracil (instead of thymine). RNA generally carries out the instructions encoded in the DNA but also executes diverse non-coding functions. RNA Types and Structure polymerase (RdRP) 
    • Small (S) fragment: encodes the viral structural proteins
• Taxonomy:
  • Family Arenaviridae
  • Genus Mammarenavirus
  • Viruses contain host ribosomes, giving the virus a granular appearance (arenosus is Latin for “sandy”).
  • Other arenaviruses include:
    • Lymphocytic choriomeningitis virus Lymphocytic Choriomeningitis Virus Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA virus transmitted to humans via rodents, the primary reservoir. Viral infections can occur through direct contact (such as through a break in the skin) with rodent urine, saliva, or droppings or via inhalation of aerosolized virus. The disease typically results in a self-limited, febrile, biphasic disease. Lymphocytic Choriomeningitis Virus ( LCMV LCMV Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA virus transmitted to humans via rodents, the primary reservoir. Viral infections can occur through direct contact (such as through a break in the skin) with rodent urine, saliva, or droppings or via inhalation of aerosolized virus. The disease typically results in a self-limited, febrile, biphasic disease. Lymphocytic Choriomeningitis Virus)
    • Junin virus (Argentine 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)
    • Machupo virus (Bolivian 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)
    • Guanarito virus (Venezuelan 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)
    • Sabia (Brazilian 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)
    • Chapare (Chapare 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)
    • Lujo (Lujo 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 in West Africa:
  • Guinea
  • Liberia
  • Sierra Leone
  • Nigeria
  • Benin
  • Ghana
  • Mali
• Higher incidence in March, when the seasons transition from dry to wet
• Morbidity and mortality:
  • Estimated 300,000 cases per year 
  • 5000 deaths annually
  • Overall case fatality rate: 1%

Pathogenesis

Reservoir and transmission

• Reservoir:
  • Multimammate rat (Mastomys natalensis)
  • Mastomys rodent infestation is commonly seen in households built with materials such as crumbling mud, which allow rodent burrows. 
• Transmission:
  • Contact with rodent(s): 
    • Direct contact with urine or feces of infected rats
    • Inhalation of aerosolized excretions of rodents
    • Consumption of infected rodents
  • Human-to-human transmission:  
    • Direct contact with the blood, urine, feces, or other bodily secretions of an infected person 
    • Viral shedding in the urine can last for up to 9 weeks
    • Sexual transmission: viral shedding in semen occurs for up to 3 months

Host risk factors

• Inhabitants in and visitors to endemic regions 
• Hospital staff (requires protective measures and proper sterilization methods)

Viral entry and disease process

• Entry via nasopharyngeal mucosa and Lassa virus targets antigen-presenting cells: 
  • Dendritic cells
  • Macrophages
  • Monocytes
• Lassa viruses primarily attach to cells with the surface G1 binding to cell receptor α-dystroglycan (α-DG). 
• The viral particle enters the cell (endocytosis) and is then engulfed by an endosome. 
• Rearrangement of the viral envelope glycoprotein complex (GPC) occurs (in low pH), leading to G2-mediated fusion of the particle with the vesicle membrane.
• This subsequently releases the viral genome into the cytoplasm for replication and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription.
• Maturation of the new viral particles takes place by budding from the host cell membrane Cell Membrane A cell membrane (also known as the plasma membrane or plasmalemma) is a biological membrane that separates the cell contents from the outside environment. A cell membrane is composed of a phospholipid bilayer and proteins that function to protect cellular DNA and mediate the exchange of ions and molecules. The Cell: Cell Membrane. 
• 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: Overview spreads to lymph nodes, and dissemination to other tissues follows.
• Macrophages and dendritic cells release mediators that cause endothelial dysfunction, impaired hemostasis Hemostasis Hemostasis refers to the innate, stepwise body processes that occur following vessel injury, resulting in clot formation and cessation of bleeding. Hemostasis occurs in 2 phases, namely, primary and secondary. Primary hemostasis involves forming a plug that stops the bleeding temporarily. Secondary hemostasis involves the activation of the coagulation cascade. Hemostasis, and reduced platelet aggregation, leading to:
  • Hepatic and/or splenic necrosis
  • Alveolar 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
  • 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
  • GI hemorrhage

Clinical Presentation

Lassa 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

• Incubation period: 6–21 days
• Approximately 80% of people who become infected have mild symptoms:
  • Low-grade fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Malaise
  • Headache
  • Improvement in 8–10 days
• Approximately 20% of infections progress further to develop:
  • Cough, sore throat, 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
  • Abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, nausea, vomiting
  • Chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain
  • Severe potentially life-threatening conditions:
    • Facial swelling
    • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion, 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
    • 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
    • Hemorrhage from the mouth, 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. Anatomy of the Nose, vagina Vagina The vagina is the female genital canal, extending from the vulva externally to the cervix uteri internally. The structures have sexual, reproductive, and urinary functions and a rich blood supply, mainly arising from the internal iliac artery. Vagina, Vulva, and Pelvic Floor, or GI tract 
    • 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
    • Renal failure
    • Shock
    • 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, tremor, disorientation, and 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

Complications and mortality

• Deafness (most common complication) in up to 30% of patients, with close to 20% developing permanent hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
• In fatal disease, death usually occurs within 2 weeks after onset of symptoms.
• In pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care:
  • Course usually severe
  • Fetal loss (> 60%) and maternal death in majority of infections that occur in the 3rd trimester
  • “Swollen baby syndrome”: 
    • Abdominal distention, anasarca, bleeding
    • Babies born to mothers infected in the 3rd trimester
• Even after recovery, viral shedding can persist for up to 3 months.

Diagnosis and Management

Tests

• Diagnostic:
  • ELISA: detects antigen, IgM, and IgG 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
  • RT- 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)
  • Culture: performed only in high-containment laboratories
•  Other lab findings:
  • CBC:
    • Leukopenia
    • 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
  • Elevated transaminases and amylase
  • Coagulation studies Coagulation studies Coagulation studies are a group of hematologic laboratory studies that reflect the function of blood vessels, platelets, and coagulation factors, which all interact with one another to achieve hemostasis. Coagulation studies are usually ordered to evaluate patients with bleeding or hypercoagulation disorders. Coagulation Studies usually normal
  • Renal function abnormality (associated with increased mortality)

Management

• Ribavirin:
  • IV preferred over oral preparation, but oral form can be given if IV is not available
  •  Shown to improve treatment outcomes when given early in the disease course
• Supportive care:
  • IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids (take precautions to avoid overload)
  • Respiratory support (oxygenation)
  • Blood transfusions as indicated

Prevention

• Currently no current effective vaccines
• Avoid rodents
• Isolation of patients
• Use of PPE in hospital or patient care settings
• Body of deceased patient should be handled properly (sealed body bag and buried by trained personnel).
• To reduce risk of sexual transmission, wait for 3 months (after resolution) before unprotected sex.
• Postexposure prophylaxis:
  • Ribavirin
  • Close monitoring

Comparison of Arenaviruses

Arenaviruses can cause hemorrhagic fevers (Lassa virus) and/or neurologic disease (lymphocytic choriomeningitis virus ( LCMV LCMV Lymphocytic choriomeningitis virus (LCMV) is a single-stranded RNA virus transmitted to humans via rodents, the primary reservoir. Viral infections can occur through direct contact (such as through a break in the skin) with rodent urine, saliva, or droppings or via inhalation of aerosolized virus. The disease typically results in a self-limited, febrile, biphasic disease. Lymphocytic Choriomeningitis Virus)).

Differential Diagnosis

Other viral hemorrhagic fevers:

• Ebola: highly contagious and potentially lethal 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 caused by Ebola virus (Filoviridae). Ebola has similar endemic regions and presentation to those for Lassa virus. Patients present with symptoms of 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, malaise, nausea, vomiting, and abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain. These symptoms can progress to hemorrhage, multiorgan failure, 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. The diagnosis is confirmed 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), serology, and electron microscopy of tissue or blood. Management is supportive.    
• Dengue Dengue Dengue is an infection caused by the Dengue virus (DENV), a small, positive-sense, single-stranded RNA virus of the genus Flavivirus. The majority of infections are asymptomatic. Symptomatic individuals may progress through 3 stages of the disease, with severe manifestations occurring in those with previous infections. Dengue Virus 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: acute febrile illness caused by the dengue virus Dengue Virus Dengue virus (DENV) is a small, positive-sense, single-stranded RNA virus of the genus Flavivirus. The infection can be transmitted to humans by the bite of female Aedes mosquitoes. The majority of infections are asymptomatic. Symptomatic individuals may progress through 3 stages of the disease, with severe manifestations occurring in those with previous infections. Dengue Virus (Flaviviridae). The virus is transmitted by Aedes aegypti mosquitoes. The majority of infections are asymptomatic. Symptomatic individuals may progress through different phases, with severe manifestations occurring in those with previous infections. The disease presents with high 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 and retro-orbital pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, myalgias and arthralgias (“breakbone” pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain), and macular or maculopapular rash. 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 can follow. The diagnosis is made by serology, antigen 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. 
• Yellow fever Yellow Fever Yellow fever is a disease caused by the yellow fever virus, a single-stranded, positive-sense RNA virus of the genus Flavivirus. Humans and primates serve as reservoirs, and transmission occurs from the bite of an infected female mosquito. Most patients present with fever and flu-like symptoms. Yellow Fever Virus: caused by the yellow fever virus Yellow Fever Virus Yellow fever is a disease caused by the yellow fever virus, a single-stranded, positive-sense RNA virus of the genus Flavivirus. Humans and primates serve as reservoirs, and transmission occurs from the bite of an infected female mosquito. Most patients present with fever and flu-like symptoms. Yellow Fever Virus (Flaviviridae). Humans and primates serve as reservoirs, and transmission occurs from the bite of an infected female mosquito. Patients 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 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. Diagnosis is by serology 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 is no antiviral treatment, so 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. 
• 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 (CCHF): zoonotic disease caused by a virus (Bunyaviridae) transmitted by ticks. Symptoms and signs 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, myalgias, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, nausea, and vomiting. Most patients recover from this illness after 1 week, but it can progress to 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 multiorgan failure. The virus is endemic in parts of Africa, the Middle East, Asia, and southeastern Europe. The diagnosis is established via RT- 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) or serology.
• Hantavirus: causes 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. Hantavirus (Bunyaviridae) is transmitted by rodents (inhalation, direct contact, or ingestion of rodent excretions). Cases are noted worldwide (Americas, Europe, Asia, Africa). Infections can cause pulmonary symptoms, hemorrhage, and renal damage from vascular endothelial injury. Diagnosis is by RT- 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) and serology. Management is supportive.

Conditions caused by other nonviral pathogens:

• Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria: mosquito-borne infectious disease caused by Plasmodium species. Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria often presents 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, rigors, diaphoresis, 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, abdominal pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, hemolytic anemia Hemolytic Anemia Hemolytic anemia (HA) is the term given to a large group of anemias that are caused by the premature destruction/hemolysis of circulating red blood cells (RBCs). Hemolysis can occur within (intravascular hemolysis) or outside the blood vessels (extravascular hemolysis). Hemolytic Anemia, hepatosplenomegaly, and renal impairment. Malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Malaria should be suspected in those with typical presentation and with residence in or travel to endemic areas (generally, tropical areas). Diagnosis is by blood smear. Rapid testing for Plasmodium antigens can also be performed. Management requires a prolonged course of multiple antimalarial drugs Antimalarial drugs Malaria, a vector-borne parasitic disease caused by Plasmodium spp., is transmitted via injection of sporozoites or immature forms of the parasite into a person's bloodstream. Sporozoites then infect the hepatocytes and differentiate into schizonts, which subsequently rupture, and merozoites invade red blood cells. Antimalarial Drugs.
• Leptospirosis Leptospirosis Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The major clinical species is Leptospira interrogans, which causes a mild flu-like illness in a majority of cases. The manifestations are biphasic, with Leptospira found in the blood initially. Leptospira/Leptospirosis: disease caused by Leptospira Leptospira Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The disease, leptospirosis, is a zoonosis, infecting animals. Rodents are the most important reservoir. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Leptospira/Leptospirosis interrogans. Bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Patients present with a mild flu-like illness in most cases, and the manifestations are biphasic. In about 10% of infections, icterohemorrhagic leptospirosis develops, manifesting as hemorrhage, renal failure, and 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. Bacterial culture takes weeks, so other 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, such as serology and dark-field microscopy are used. Treatment is primarily with penicillin.