Epidemic Typhus

Overview

Definition

Epidemic typhus is a potentially lethal, febrile illness caused by the obligate intracellular gram-negative bacterium, Rickettsia prowazekii Rickettsia prowazekii A species of gram-negative, aerobic bacteria that is the etiologic agent of epidemic typhus fever acquired through contact with lice as well as brill’s disease. Rickettsia.

Epidemiology

Transmission:

• Typhus is transmitted by infected lice.
• 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 occur in winter Winter Pityriasis Rosea or spring.

Risk factors:

• Overcrowded conditions:
  • Reported in army camps, refugee camps, prisons, and homeless shelters
  • Sometimes called “jail fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever”
• Poor hygiene: 
  • Civil strife
  • War zones
• Malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries:
  • Famine
  • Extreme poverty

Geography:

• In the US:
  • Rare
  • Cases often associated with exposure to flying squirrels
• Epidemic typhus outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza have been reported in the following countries:
  • Africa:
    • Ethiopia
    • Nigeria
    • Rwanda
    • Burundi
  • Mexico
  • Central America
  • South America
  • Eastern Europe
  • Afghanistan
  • Russia
  • Northern India
  • China

Etiology and Pathophysiology

Etiology

• Causative agent: R. prowazekii is the most pathogenic member of the Rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia genus.
• Vector:
  • Human body louse, Pediculus humanus Pediculus humanus Lice of the genus pediculus, family pediculidae. Pediculus humanus corporis is the human body louse and pediculus humanus capitis is the human head louse. Bartonella corporis
  • Human head louse, P. humanus capitis
• 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:
  • Humans
  • Flying squirrels
• Transmission:
  • Infected lice pass infectious feces when they feed.
  • The feces and not the bite of the louse spread illness in humans.
  • Transmitted when the infectious feces of lice or crushed, infected body lice are rubbed into small cuts or abrasions Abrasions Corneal Abrasions, Erosion, and Ulcers on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
  • The disease may also be spread when: 
    • A person breathes in dust containing infected dried feces of lice
    • Mucous membranes, such as the conjunctiva Conjunctiva The mucous membrane that covers the posterior surface of the eyelids and the anterior pericorneal surface of the eyeball. Eye: Anatomy of the eye, are exposed to infectious feces

Pathophysiology

• After entering the body, Rickettsia Rickettsia Rickettsiae are a diverse collection of obligate intracellular, gram-negative bacteria that have a tropism for vascular endothelial cells. The vectors for transmission vary by species but include ticks, fleas, mites, and lice. Rickettsia infect and multiply in the endothelial cells of the small venous, arterial, and capillary vessels.
• Infected endothelial cells enlarge due to microbial proliferation.
• Multiorgan vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus develops.
• Vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus can lead to: 
  • Thrombosis of the supplying blood vessels: gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction of the distal parts of the extremities, 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), ear lobes, and genitalia
  • Deposition of leukocytes Leukocytes White blood cells. These include granular leukocytes (basophils; eosinophils; and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). White Myeloid Cells: Histology, 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 platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology results in the formation of small nodules.
  • Increased vascular permeability:
    • Loss of intravascular colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids with subsequent hypovolemia Hypovolemia Sepsis in Children
    • Loss of electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes 
    • Decreased tissue perfusion → organ failure

Clinical Presentation

• Incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus period: usually < 14 days
• Clinical manifestations:
  • General:
    • 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
    • Severe 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
    • Rash Rash Rocky Mountain Spotted Fever (a pink macular rash Rash Rocky Mountain Spotted Fever that spares the palms and soles)
    • Chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever
    • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
    • Arthralgias
    • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
    • Nonproductive cough
  • GI:
    • 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
    • Abdominal pain Abdominal Pain Acute Abdomen
    • Vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
    • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
• Severe epidemic typhus can lead to:
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Gangrene Gangrene Death and putrefaction of tissue usually due to a loss of blood supply. Small Bowel Obstruction
  • Loss of digits, limbs, or other appendages
  • CNS dysfunction (ranging from decreased mentation to 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)
  • Multiorgan system failure
  • Death
• Brill-Zinsser disease:
  • Recrudescence of epidemic typhus following an initial attack
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship can have a prolonged, asymptomatic R. prowazekii infection for years.
  • A relapse Relapse Relapsing Fever that occurs months or years following the 1st illness, when the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs is weakened due to certain medications, advanced age, or illness
  • Symptoms are similar to the original infection, but usually milder.

Diagnosis and Management

Diagnosis

• Epidemic typhus is diagnosed by its clinical features in the setting of a louse infection.
• Confirmatory laboratory tests:
  • Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma of rash Rash Rocky Mountain Spotted Fever using fluorescent antibody staining to determine the causative microbe
  • Acute and convalescent serologic testing
  • 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

Antibiotics:

• Primary treatment: doxycycline (4 mg/kg/day)
• Alternative treatments:
  • Tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury (25–50 mg/kg/day)
  • Chloramphenicol Chloramphenicol Chloramphenicol, the only clinically relevant drug in the amphenicol class, is a potent inhibitor of bacterial protein synthesis by binding to the 50S ribosomal subunit and preventing peptide bond formation. Chloramphenicol is a broad-spectrum antibiotic with wide distribution; however, due to its toxicity, its use is limited to severe infections. Chloramphenicol 500 mg orally or IV 4 times daily for 7 days 

Prevention:

• Louse control:
  • Lice may be eliminated by dusting infested individuals with malathion Malathion A wide spectrum aliphatic organophosphate insecticide widely used for both domestic and commercial agricultural purposes. Cholinomimetic Drugs or lindane.
  • Washing of clothing in hot water 
  • Sweeping off dust particles, as they contain excreta of infected lice
• Immunization is highly effective for prevention; however, typhus vaccines are no longer available in the US.
• Antibiotic prophylaxis Prophylaxis Cephalosporins with doxycycline (once weekly) for individuals traveling to high-risk areas

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas:

• Mortality Mortality All deaths reported in a given population. Measures of Health Status rate of untreated epidemic typhus:
  • 20% in otherwise healthy individuals 
  • 60% in the elderly or in debilitated individuals
• When treated with appropriate antibiotics, the mortality Mortality All deaths reported in a given population. Measures of Health Status rate can decrease to approximately 3%–4%.

Differential Diagnosis

• Rocky Mountain spotted 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 ( RMSF RMSF Rocky mountain spotted fever (RMSF) is a bacterial infection caused by the obligate intracellular parasite rickettsia rickettsii. Transmission occurs through an arthropod vector, most commonly the american dog tick (dermacentor variabilis). Early signs and symptoms of rmsf are nonspecific and include a high fever, severe headache, and rash. Rocky Mountain Spotted Fever): a disease caused by R. rickettsii and transmitted by ixodid ticks Ticks Blood-sucking acarid parasites of the order ixodida comprising two families: the softbacked ticks (argasidae) and hardbacked ticks (ixodidae). Ticks are larger than their relatives, the mites. They penetrate the skin of their host by means of highly specialized, hooked mouth parts and feed on its blood. Ticks attack all groups of terrestrial vertebrates. In humans they are responsible for many tick-borne diseases, including the transmission of rocky mountain spotted fever; tularemia; babesiosis; african swine fever; and relapsing fever. Coxiella/Q Fever. The 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 is highest in children < 15 years and in individuals who frequent tick-infested areas for work or recreation. Rocky Mountain spotted 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 presents with abrupt headaches, chills Chills The sudden sensation of being cold. It may be accompanied by shivering. Fever, prostration, muscular pains, and centripetal rash Rash Rocky Mountain Spotted Fever, and is diagnosed based on clinical features, 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). Treatment is using doxycycline.
• Kawasaki disease Kawasaki disease An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities. Kawasaki Disease: an acute febrile illness of early childhood of unknown cause. Kawasaki disease Kawasaki disease An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities. Kawasaki Disease is the leading cause of acquired coronary artery Coronary Artery Truncus Arteriosus disease in developed nations and is characterized by vasculitis Vasculitis Inflammation of any one of the blood vessels, including the arteries; veins; and rest of the vasculature system in the body. Systemic Lupus Erythematosus of the medium-sized arteries Medium-Sized Arteries Kawasaki Disease, especially coronary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology. Other features of Kawasaki disease Kawasaki disease An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities. Kawasaki Disease include rashes Rashes Rashes are a group of diseases that cause abnormal coloration and texture to the skin. The etiologies are numerous but can include irritation, allergens, infections, or inflammatory conditions. Rashes that present in only 1 area of the body are called localized rashes. Generalized rashes occur diffusely throughout the body. Generalized and Localized Rashes on the extremities, oropharyngeal rash Rash Rocky Mountain Spotted Fever, and bulbar 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, as well as acute, unilateral, nonpurulent cervical lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. The diagnosis is made on clinical grounds and the diagnostic test of choice is echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA). The mainstays of treatment are aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs) and IV Igs Igs 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. 
• Anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax: a disease caused by the gram-positive Gram-Positive Penicillins microbe Bacillus anthracis Bacillus anthracis A species of bacteria that causes anthrax in humans and animals. Anthrax. Anthrax Anthrax Anthrax is an infection caused by the bacterium Bacillus anthracis, which usually targets the skin, lungs, or intestines. Anthrax is a zoonotic disease and is usually transmitted to humans from animals or through animal products. Symptoms depend on which organ system is affected. Anthrax is transmitted to humans when they come in contact with infected animals Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, animalia was one of the kingdoms. Under the modern three domain model, animalia represents one of the many groups in the domain eukaryota. Cell Types: Eukaryotic versus Prokaryotic or their products. Cutaneous anthrax Cutaneous anthrax Bacillus begins as a painless, pruritic, red-brown papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes 1–10 days after exposure to infective spores Spores The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Anthrax. The papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes can enlarge, become necrotic, and form a black eschar. The diagnosis is made through clinical findings and is based on occupational and exposure history. Confirmatory laboratory tests include Gram staining Gram staining Bacteriology and culture, direct fluorescent antibody Direct Fluorescent Antibody A form of fluorescent antibody technique utilizing a fluorochrome conjugated to an antibody, which is added directly to a tissue or cell suspension for the detection of a specific antigen. Congenital TORCH Infections test, 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). Empiric treatment is using ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones, levofloxacin Levofloxacin The l-isomer of ofloxacin. Fluoroquinolones, moxifloxacin Moxifloxacin A fluoroquinolone that acts as an inhibitor of DNA topoisomerase II and is used as a broad-spectrum antibacterial agent. Fluoroquinolones, or doxycycline.