Lassa Virus

Classification

General Characteristics

Basic features

• Enveloped
• Spherical
• Medium-sized agent, measuring 70–150 nm in diameter
• 2 viral surface glycoproteins Surface glycoproteins Glycoproteins found on the membrane or surface of cells. Human Herpesvirus 8 on 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: 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 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:
  • Encapsulated Encapsulated Klebsiella by a 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) nucleocapsid
  • Segmented single-stranded, negative-sense RNA Negative-sense RNA RNA viruses that have their genetic material encoded in the form of single-stranded, negative-sense RNA. Unlike retroviruses they do not employ DNA intermediates in their life-cycle. Respiratory Syncytial Virus, made of:
    • Large (L) fragment: encodes the RNA-dependent RNA polymerase RNA-dependent RNA polymerase An enzyme that catalyses rna-template-directed extension of the 3′- end of an RNA strand by one nucleotide at a time, and can initiate a chain de novo. Virology (RdRP) 
    • Small (S) fragment: encodes the viral structural proteins Structural proteins Proteins and Peptides
• Taxonomy:
  • Family Arenaviridae
  • Genus Mammarenavirus
  • 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 contain host ribosomes Ribosomes Multicomponent ribonucleoprotein structures found in the cytoplasm of all cells, and in mitochondria, and plastids. They function in protein biosynthesis via genetic translation. The Cell: Organelles, giving 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 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 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 (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 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 (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 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 (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 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 in March, when the seasons transition from dry to wet
• Morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status:
  • Estimated 300,000 cases per year 
  • 5000 deaths annually
  • Overall case fatality rate Case fatality rate Defined as the number of deaths of individuals with a certain disease or condition divided by the total number of people diagnosed with that same disease or condition over a specific time period. Measures of Health Status: 1%

Pathogenesis

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 and transmission

• 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:
  • Multimammate rat (Mastomys natalensis)
  • Mastomys rodent infestation is commonly seen in households built with materials such as crumbling mud, which allow rodent burrows Burrows Dermatologic Examination. 
• 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 Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus in the urine can last for up to 9 weeks
    • Sexual transmission: viral shedding Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus 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 Sterilization Procedures to block or remove all or part of the genital tract for the purpose of rendering individuals sterile, incapable of reproduction. Surgical sterilization procedures are the most commonly used. There are also sterilization procedures involving chemical or physical means. Reproductive Ethical Issues methods)

Viral entry and disease process

• Entry via nasopharyngeal mucosa and Lassa 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 targets antigen-presenting cells Antigen-presenting cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include macrophages; dendritic cells; langerhans cells; and B-lymphocytes. Follicular dendritic cells are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of immune complexes for b-cell recognition they are considered so by some authors. Adaptive Immune Response: 
  • 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
  • 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
  • Monocytes Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Innate Immunity: Phagocytes and Antigen Presentation
• Lassa 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 primarily attach to cells with the surface G1 binding to cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors α-dystroglycan (α-DG). 
• The viral particle enters the cell ( endocytosis Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. The Cell: Cell Membrane) and is then engulfed by an endosome Endosome Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. Hepatitis C Virus. 
• Rearrangement of the viral 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 glycoprotein complex (GPC) occurs (in low pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance), leading to G2-mediated fusion of the particle with the vesicle Vesicle Primary Skin Lesions membrane.
• This subsequently releases the viral genome Viral genome The complete genetic complement contained in a DNA or RNA molecule in a virus. Virology 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 Budding Mycology 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 spreads to lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy, and dissemination to other tissues follows.
• 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 release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology 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 Platelet 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. Hemostasis, leading to:
  • Hepatic and/or splenic necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • 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 Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: 6–21 days
• Approximately 80% of people who become infected have mild symptoms:
  • Low-grade fever Low-Grade Fever Erythema Infectiosum
  • Malaise Malaise Tick-borne Encephalitis Virus
  • 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
  • Improvement in 8–10 days
• Approximately 20% of 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 progress further to develop:
  • Cough, sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis, 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 Abdominal Pain Acute Abdomen, 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
  • Chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways
  • Severe potentially life-threatening conditions:
    • Facial swelling Swelling Inflammation
    • 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. Nose Anatomy (External & Internal), 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: Anatomy, 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 Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome
    • 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
    • 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 Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies, disorientation Disorientation St. Louis Encephalitis Virus, 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 Mortality All deaths reported in a given population. Measures of Health Status

• Deafness (most common complication) in up to 30% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, 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 The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
  • Course usually severe
  • Fetal loss (> 60%) and maternal death in majority of 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 that occur in the 3rd trimester
  • “Swollen baby syndrome”: 
    • Abdominal distention Abdominal distention Megacolon, anasarca Anasarca Hookworm Infections, bleeding
    • Babies born to mothers infected in the 3rd trimester
• Even after recovery, viral shedding Viral shedding The expelling of virus particles from the body. Important routes include the respiratory tract, genital tract, and intestinal tract. Hepatitis A Virus can persist for up to 3 months.

Diagnosis and Management

Tests

• Diagnostic:
  • 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: detects antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination, 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 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
  • 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)
  • 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 Transaminases A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. Autoimmune Hepatitis and amylase Amylase A group of amylolytic enzymes that cleave starch, glycogen, and related alpha-1, 4-glucans. Digestion and Absorption
  • 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 Mortality All deaths reported in a given population. Measures of Health Status)

Management

• 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:
  • 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 Blood transfusions The introduction of whole blood or blood component directly into the bloodstream. Transfusion Products as indicated

Prevention

• Currently no current effective vaccines
• Avoid rodents
• Isolation of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• 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 Unprotected sex HIV Infection and AIDS.
• Postexposure prophylaxis Prophylaxis Cephalosporins:
  • 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
  • Close monitoring

Comparison of Arenaviruses

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

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 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 ( Filoviridae Filoviridae A family of RNA viruses, of the order mononegavirales, containing filamentous virions. Although they resemble rhabdoviridae in possessing helical nucleocapsids, filoviridae differ in the length and degree of branching in their virions. There are two genera: ebolavirus and marburgvirus. Ebolavirus and Marburgvirus). Ebola has similar endemic regions and presentation to those for Lassa 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. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Malaise Tick-borne Encephalitis Virus, 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, and abdominal pain Abdominal Pain Acute Abdomen. 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 Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus, and electron microscopy of tissue or blood. Management is supportive.    
• Dengue hemorrhagic fever Dengue hemorrhagic fever Dengue Virus: acute febrile illness caused by the 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 ( Flaviviridae Flaviviridae A family of RNA viruses, many of which cause disease in humans and domestic animals. There are three genera flavivirus; pestivirus; and hepacivirus, as well as several unassigned species. Hepatitis C Virus). 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 by Aedes aegypti mosquitoes. The majority of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are asymptomatic. Symptomatic individuals may progress through different phases, 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 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 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 macular or maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever. 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 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. 
• Yellow 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 the yellow 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 ( Flaviviridae Flaviviridae A family of RNA viruses, many of which cause disease in humans and domestic animals. There are three genera flavivirus; pestivirus; and hepacivirus, as well as several unassigned species. Hepatitis C 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. Diagnosis is by 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 is no antiviral Antiviral Antivirals for Hepatitis B 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 Crimean-Congo hemorrhagic fever A severe, often fatal disease in humans caused by the crimean-Congo hemorrhagic fever virus. Bunyavirales (CCHF): zoonotic disease caused by a 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 ( Bunyaviridae Bunyaviridae A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: orthobunyavirus; hantavirus; nairovirus; phlebovirus; and tospovirus. Bunyavirales) transmitted by 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. 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 Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus, abdominal pain Abdominal Pain Acute Abdomen, 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, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 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 endemic in parts of Africa, the Middle East, Asia ASIA Spinal Cord Injuries, and southeastern Europe. The diagnosis is established via RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) or serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus.
• Hantavirus Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales: 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 Hantavirus A genus of the family bunyaviridae causing hantavirus infections, first identified during the korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. Hantaan virus is the type species. Bunyavirales ( Bunyaviridae Bunyaviridae A family of viruses, mainly arboviruses, consisting of a single strand of RNA. Virions are enveloped particles 90-120 nm diameter. The complete family contains over 300 members arranged in five genera: orthobunyavirus; hantavirus; nairovirus; phlebovirus; and tospovirus. Bunyavirales) is transmitted by rodents (inhalation, direct contact, or ingestion of rodent excretions). Cases are noted worldwide (Americas, Europe, Asia ASIA Spinal Cord Injuries, Africa). 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 can cause pulmonary symptoms, hemorrhage, and renal damage from vascular endothelial injury. Diagnosis is by RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) and serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus. 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. Plasmodium/Malaria: mosquito-borne infectious disease caused by Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs 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. Plasmodium/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 Rigors Fever, 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 Abdominal Pain Acute Abdomen, 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 Hepatosplenomegaly Cytomegalovirus, 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. Plasmodium/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 Blood smear Myeloperoxidase Deficiency. Rapid testing for Plasmodium Plasmodium A genus of protozoa that comprise the malaria parasites of mammals. Four species infect humans (although occasional infections with primate malarias may occur). These are plasmodium falciparum; plasmodium malariae; plasmodium ovale, and plasmodium vivax. Species causing infection in vertebrates other than man include: plasmodium berghei; plasmodium chabaudi; p. Vinckei, and plasmodium yoelii in rodents; p. Brasilianum, plasmodium cynomolgi; and plasmodium knowlesi in monkeys; and plasmodium gallinaceum in chickens. Antimalarial Drugs 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 interrogans Leptospira interrogans A genus of question mark-shaped bacteria spirochetes which is found in freshwater that is contaminated by animal urine. It causes leptospirosis. Leptospira/Leptospirosis. 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 shed in the urine of rodents and other 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 can be transmitted to humans via contaminated water. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with a mild flu-like illness in most cases, and the manifestations are biphasic. In about 10% of 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, icterohemorrhagic leptospirosis Icterohemorrhagic leptospirosis Leptospira/Leptospirosis develops, manifesting as hemorrhage, renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome, 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 Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus and dark-field microscopy Dark-field microscopy Treponema are used. Treatment is primarily with penicillin Penicillin Rheumatic Fever.