Rickettsia rickettsii
Encyclopedia
Rickettsia rickettsii (abbreviated as R. rickettsii) is a unicellular, gram-negative coccobacillus (plural coccobacilli) that is native to the New World
. It belongs to the spotted fever group (SFG) of Rickettsia and is most commonly known as the causative agent of Rocky Mountain spotted fever
(RMSF). By nature, R. rickettsii is an obligate intracellular parasite
that survive by an endosymbiotic relationship with other cells.
R. rickettsii is a non-motile, non-spore forming aerobic organism. Cells are typically 0.3-0.5 X 0.8-2.0 um in size. They lack a distinct nucleus and membrane bound organelles. Their outer membrane is composed mostly lipopolysaccharides.
RMSF is transmitted by the bite of an infected tick
while feeding on warm-blooded animals, including humans. Humans are considered to be accidental hosts in the rickettsia–tick life cycle and are not required to maintain the rickettsiae in nature.
Howard Ricketts (1871-1910) was an American pathologist and infectious disease researcher who was the first to identify and study the organism that causes Rocky Mountain spotted fever. He received his undergraduate degree in zoology from the University of Nebraska and his medical degree from Northwestern University School of Medicine. Rickets completed his internship at Cook County Hospital in Chicago, IL, followed by a fellowship in pathology and cutaneous diseases at Rush Medical College.
In 1902, Ricketts became the associate professor of pathology at the University of Chicago. The trademark rash, which first appeared in the Idaho Valley, now began to slowly emerge in the Bitterroot Valley
region, a highly influential area in western Montana and had an 80-90% mortality rate. During his tenure as associate professor, Ricketts was funded and recruited by the University of Chicago
, the State of Montana
, and the American Medical Association
to conduct research on Rocky Mountain spotted fever.
His research entailed interviewing victims of the disease and collecting and studying infected animals. He was also known to inject himself with pathogens to measure its effects.
Ricketts was also known for his research on typhus
, which was very similar to spotted fever. Ironically, days after isolating the organism that he believed to cause typhus, he died. It was speculated that his death was likely caused from an insect bite.
In 1922, French pathologist, Dr. Emile Brumpt, proposed the name Rickettsia rickettsia, in honor of Howard Ricketts.
S. Burt Wolbach is credited for the first detailed description of the etiologic agent in 1919. He clearly recognized it as an intracellular bacterium which was seen most frequently in endothelial cells. He was struck by the fact that in the tick, and also in mammalian cells, the microorganism was intranuclear. The nucleus
was often completely filled with minute particles and often was distended. Although Wolbach recognized its similarity to the agent of typhus
and tsutsugamushi fever (scrub typhus), he did not regard the designation 'rickettsia' as appropriate. He proposed the name Dermacentroxenus rickettsi. Emile Brumpt
felt that the etiologic agent of RMSF, despite some uncertainty about its properties, belonged in the genus Rickettsia and in 1922 proposed the name Rickettsia rickettsii.
Rickettsia rickettsii mostly affects canines and humans.
First, an uninfected tick can become infected when feeding on the blood of an infected mammalian host in the larval or nymph stages, a mode of transmission called "transstadial transmission". Once a tick becomes infected with this pathogen, they are infected for life. Both the American dog tick and the Rocky Mountain wood tick serve as long-term reservoirs for Rickettsia rickettsii, in which the organism resides in the tick posterior diverticulae of the midgut, the small intestine and the ovaries.
Due to its confinement in the midgut and small intestine, it is possible for mammals, including humans, to contract rickettsial disease from open skin/wound contact with the feces of the organism. In addition, an infected male tick can transmit the organism to an uninfected female during mating. Once infected, the female tick can transmit the infection to her offspring, in a process known as "transovarial transmission".
Humans acquire Rickettsia rickettsii infection from infected vectors. After getting bitten by an infected tick, rickettsiae are transmitted to the bloodstream by tick salivary secretions or, as mentioned previously, through contamination of broken skin by infected vector feces.
All these modes of transmission ensures the survival of Rickettsia in nature.
R. rickettsii have evolved a number of strategical mechanisms or virulence
factors that allow them to evade the host immune system and successfully infect the host.
that induces phagocytosis. They are able to avoid lysosomal fusion and oxidative burst by escaping from the phagosome
into the cytoplasm where they multiply and spread.
Over the years, different virulence factors have been identified in R. rickettsii.
rOmp B is the predominant surface membrane protein in R. rickettsii; Policastro et al, identified the rOmpA to rOmpB ratio to be 1:9 (1994). While the surface proteins of the bacterium have been identified, the host cell protein receptor(s) have not.
-dependent process that results in the direct transfer of the bacterium's DNA
and other proteins into the host cell.
and into the cytosol where replication
takes place. Although the escape from the phagosome is not well understood, it is thought to be mediated by phospholipase A2 activity.
is a bacterial surface protein that is associated with actin nucleation and tail formation in R. rickettsii. After interacting with the host cytoskeletal proteins, the bacterium develops an actin tail. The actin-based motility of R. rickettsii allows swift, unidirectional movement across the cytoplasm into adjacent cells, promoting cell to cell spread.
Endothelial cell damage caused by R. rickettsii can lead to end organ failure, DIC, and even death.
studies reveal that Rickettsia rickettsii invade endothelial lining of small to medium vessels in the human host, causing vascular permeability. When tested in vitro
, it is shown that the bacterium infects every kind of cell of the mammalian host.
is limited to regions of the United States in proximity to the Rocky Mountains
(the mountainous regions encompassing the northern most part of British Columbia to southwestern United States); however, the name RMSF is somewhat of a misnomer. Cases of Rocky Mountain spotted fever have been reported in every continent except Antarctica, and in every state in the U.S. except for Maine
, Alaska
, and Hawaii
.
Approximately 90% of all infections occur within the months of April to September, the time period in which adult and nymphal ticks are the highest. The areas of the U.S. with the greatest reported cases of RMSF are the mid to south Atlantic states, including DE, MD, DC, VA, WV, NC, SC.
It is estimated that approximately 1200 or more new cases of RMSF will present on a yearly basis.
states that the diagnosis of RMSF must be made based on the clinical signs and symptoms of the patient and later confirmed using specialized laboratory tests. However, the diagnosis of RMSF is often missed due to its non-specific onset. The clinical signs and symptoms that a patient may experience could appear and may be misdiagnosed as other diseases even by the most experienced physician.
(CDC). The IFA will detect an increase in IgG or IgM
antibodies.
A more specific lab test used in diagnosing RMSF is polymerase chain reaction
or PCR which can detect the presence of rickettiae DNA.
Immunohistochemical (IHC) staining is another diagnostic approach where a skin biopsy is taken of the spotted rash; however, sensitivity is only 70%.
and Chloramphenicol
are the most common drugs of choice for reducing the symptoms associated with RMSF. When it is suspected that a patient may have RMSF, it is crucial that antibiotic therapy be administered promptly. Failure to receive antibiotic therapy, especially during the initial stages of the disease, may lead to end-organ failure (heart, kidney, lungs, meningitis
, brain damage
, shock, and even death.
New World
The New World is one of the names used for the Western Hemisphere, specifically America and sometimes Oceania . The term originated in the late 15th century, when America had been recently discovered by European explorers, expanding the geographical horizon of the people of the European middle...
. It belongs to the spotted fever group (SFG) of Rickettsia and is most commonly known as the causative agent of Rocky Mountain spotted fever
Rocky Mountain spotted fever
Rocky Mountain spotted fever is the most lethal and most frequently reported rickettsial illness in the United States. It has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” , “São Paulo fever” or “febre...
(RMSF). By nature, R. rickettsii is an obligate intracellular parasite
Obligate intracellular parasite
Intracellular parasites are parasitic microorganisms - microparasites that are capable of growing and reproducing inside the cells of a host.-Facultative:...
that survive by an endosymbiotic relationship with other cells.
R. rickettsii is a non-motile, non-spore forming aerobic organism. Cells are typically 0.3-0.5 X 0.8-2.0 um in size. They lack a distinct nucleus and membrane bound organelles. Their outer membrane is composed mostly lipopolysaccharides.
RMSF is transmitted by the bite of an infected tick
Tick
Ticks are small arachnids in the order Ixodida, along with mites, constitute the subclass Acarina. Ticks are ectoparasites , living by hematophagy on the blood of mammals, birds, and sometimes reptiles and amphibians...
while feeding on warm-blooded animals, including humans. Humans are considered to be accidental hosts in the rickettsia–tick life cycle and are not required to maintain the rickettsiae in nature.
History
Rocky Mountain spotted fever first emerged in the Idaho Valley in 1896. At that time, not much information was known about the disease; it was originally called Black Measles because patients had a characteristic spotted rash appearance throughout their body.Howard Ricketts (1871-1910) was an American pathologist and infectious disease researcher who was the first to identify and study the organism that causes Rocky Mountain spotted fever. He received his undergraduate degree in zoology from the University of Nebraska and his medical degree from Northwestern University School of Medicine. Rickets completed his internship at Cook County Hospital in Chicago, IL, followed by a fellowship in pathology and cutaneous diseases at Rush Medical College.
In 1902, Ricketts became the associate professor of pathology at the University of Chicago. The trademark rash, which first appeared in the Idaho Valley, now began to slowly emerge in the Bitterroot Valley
Bitterroot Valley
The Bitterroot Valley is located in southwestern Montana in the northwestern United States. It extends over 100 miles from remote Horse Creek Pass north to a point near the city of Missoula...
region, a highly influential area in western Montana and had an 80-90% mortality rate. During his tenure as associate professor, Ricketts was funded and recruited by the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...
, the State of Montana
Montana
Montana is a state in the Western United States. The western third of Montana contains numerous mountain ranges. Smaller, "island ranges" are found in the central third of the state, for a total of 77 named ranges of the Rocky Mountains. This geographical fact is reflected in the state's name,...
, and the American Medical Association
American Medical Association
The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...
to conduct research on Rocky Mountain spotted fever.
His research entailed interviewing victims of the disease and collecting and studying infected animals. He was also known to inject himself with pathogens to measure its effects.
Ricketts was also known for his research on typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
, which was very similar to spotted fever. Ironically, days after isolating the organism that he believed to cause typhus, he died. It was speculated that his death was likely caused from an insect bite.
In 1922, French pathologist, Dr. Emile Brumpt, proposed the name Rickettsia rickettsia, in honor of Howard Ricketts.
S. Burt Wolbach is credited for the first detailed description of the etiologic agent in 1919. He clearly recognized it as an intracellular bacterium which was seen most frequently in endothelial cells. He was struck by the fact that in the tick, and also in mammalian cells, the microorganism was intranuclear. The nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
was often completely filled with minute particles and often was distended. Although Wolbach recognized its similarity to the agent of typhus
Typhus
Epidemic typhus is a form of typhus so named because the disease often causes epidemics following wars and natural disasters...
and tsutsugamushi fever (scrub typhus), he did not regard the designation 'rickettsia' as appropriate. He proposed the name Dermacentroxenus rickettsi. Emile Brumpt
Emile Brumpt
Alexandre Joseph Emile Brumpt was a French parasitologist who was born in Paris. He studied zoology and parasitology in Paris, obtaining his degree in science in 1901, and his medical doctorate in 1906. In 1919 he became a professor to the Faculté de Médecine, as well as director of the...
felt that the etiologic agent of RMSF, despite some uncertainty about its properties, belonged in the genus Rickettsia and in 1922 proposed the name Rickettsia rickettsii.
Pathogen life cycle
The life cycle of Rickettsia rickettsii is considered to be a complex one. Survival is dependent on both an invertebrate vector, (the hard tick- Family Ixodidae) and a vertebrate host (including mice, dogs, rabbits). Humans are considered to be accidental vectors and are not essential in the rickettsial cycle. In addition, a sequence of events occur between both hosts in the successful transmission of rickettsial disease.
Rickettsia rickettsii mostly affects canines and humans.
Transmission in arthropod vectors
Three arthropod vectors in the United States have been identified in transmitting R. rickettsii to humans, causing the potentially fatal disease Rocky Mountain Spotted Fever. The American dog tick (Dermacentor variabilis), the Rocky Mountain Wood Tick (Dermacentor andersoni), and the Brown dog tick (Rhipicephalus sanguineus) can acquire Rickettsia rickettsii in a number of different ways.First, an uninfected tick can become infected when feeding on the blood of an infected mammalian host in the larval or nymph stages, a mode of transmission called "transstadial transmission". Once a tick becomes infected with this pathogen, they are infected for life. Both the American dog tick and the Rocky Mountain wood tick serve as long-term reservoirs for Rickettsia rickettsii, in which the organism resides in the tick posterior diverticulae of the midgut, the small intestine and the ovaries.
Due to its confinement in the midgut and small intestine, it is possible for mammals, including humans, to contract rickettsial disease from open skin/wound contact with the feces of the organism. In addition, an infected male tick can transmit the organism to an uninfected female during mating. Once infected, the female tick can transmit the infection to her offspring, in a process known as "transovarial transmission".
Transmission in mammals
An uninfected mammal can become infected with Rickettsia rickettsii when eating food that contains the feces of the infected tick. They can also succumb to infection through the bite of an infected tick.Humans acquire Rickettsia rickettsii infection from infected vectors. After getting bitten by an infected tick, rickettsiae are transmitted to the bloodstream by tick salivary secretions or, as mentioned previously, through contamination of broken skin by infected vector feces.
All these modes of transmission ensures the survival of Rickettsia in nature.
R. rickettsii have evolved a number of strategical mechanisms or virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
factors that allow them to evade the host immune system and successfully infect the host.
Virulence
R. rickettsii invades the endothelial cells that line the blood vessels. Endothelial cells are not phagocytic in nature; however, after attachment to the host cell surface, the pathogen causes changes in the host cell cytoskeletonCytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
that induces phagocytosis. They are able to avoid lysosomal fusion and oxidative burst by escaping from the phagosome
Phagosome
In cell biology, a phagosome is a vacuole formed around a particle absorbed by phagocytosis. The vacuole is formed by the fusion of the cell membrane around the particle. A phagosome is a cellular compartment in which pathogenic microorganisms can be killed and digested...
into the cytoplasm where they multiply and spread.
Over the years, different virulence factors have been identified in R. rickettsii.
OmpA and OmpB
OmpA (rOmp) and Omp B (rOmp) have been identified as rickettsial outer surface proteins and are implicated in adherence of the bacterium to the host cell. The genes that encode these two surface proteins are designated as ompA and ompB, respectively.rOmp B is the predominant surface membrane protein in R. rickettsii; Policastro et al, identified the rOmpA to rOmpB ratio to be 1:9 (1994). While the surface proteins of the bacterium have been identified, the host cell protein receptor(s) have not.
T4SS
Entry into the host cell is medicated by a Type 4 secretion system' (T4SS) which is found in all rickettsiae. The organization of the T4SS apparatus is a rather elaborate one; it is a tunnel-shaped structure that is embedded in the bacterial inner membrane and extends to the outer membrane. At least 12 or more proteins help form the tunnel-like apparatus. Once adherence to the host cell is established, the T4SS of rickettsiae recruits substrates to the bottom of the apparatus, activating the complex via an ATPAdenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
-dependent process that results in the direct transfer of the bacterium's DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and other proteins into the host cell.
Phospholipase A2
Invasion of the host endothelial cell immediately triggers phagocytosis, where the rickettsiae escape from the phagosomePhagosome
In cell biology, a phagosome is a vacuole formed around a particle absorbed by phagocytosis. The vacuole is formed by the fusion of the cell membrane around the particle. A phagosome is a cellular compartment in which pathogenic microorganisms can be killed and digested...
and into the cytosol where replication
Replication
Replication may refer to:Science* Replication is one of the main principles of the scientific method, a.k.a. reproducibility** Replication , the repetition of a test or complete experiment...
takes place. Although the escape from the phagosome is not well understood, it is thought to be mediated by phospholipase A2 activity.
Actin polymerization
In the cytosol, another virulence factor, ActA, allows survival of the bacterium. ActAActa
ACTA may refer to:* Administrative Council for Terminal Attachments, a standards organization for terminal equipment such as registered jacks* Alameda Corridor Transportation Authority, in southern California...
is a bacterial surface protein that is associated with actin nucleation and tail formation in R. rickettsii. After interacting with the host cytoskeletal proteins, the bacterium develops an actin tail. The actin-based motility of R. rickettsii allows swift, unidirectional movement across the cytoplasm into adjacent cells, promoting cell to cell spread.
Endothelial cell damage caused by R. rickettsii can lead to end organ failure, DIC, and even death.
In vivo versus in vitro studies
In vivoIn vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
studies reveal that Rickettsia rickettsii invade endothelial lining of small to medium vessels in the human host, causing vascular permeability. When tested in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
, it is shown that the bacterium infects every kind of cell of the mammalian host.
Epidemiology
As the name may imply, Rocky Mountain spotted feverRocky Mountain spotted fever
Rocky Mountain spotted fever is the most lethal and most frequently reported rickettsial illness in the United States. It has been diagnosed throughout the Americas. Some synonyms for Rocky Mountain spotted fever in other countries include “tick typhus,” “Tobia fever” , “São Paulo fever” or “febre...
is limited to regions of the United States in proximity to the Rocky Mountains
Rocky Mountains
The Rocky Mountains are a major mountain range in western North America. The Rocky Mountains stretch more than from the northernmost part of British Columbia, in western Canada, to New Mexico, in the southwestern United States...
(the mountainous regions encompassing the northern most part of British Columbia to southwestern United States); however, the name RMSF is somewhat of a misnomer. Cases of Rocky Mountain spotted fever have been reported in every continent except Antarctica, and in every state in the U.S. except for Maine
Maine
Maine is a state in the New England region of the northeastern United States, bordered by the Atlantic Ocean to the east and south, New Hampshire to the west, and the Canadian provinces of Quebec to the northwest and New Brunswick to the northeast. Maine is both the northernmost and easternmost...
, Alaska
Alaska
Alaska is the largest state in the United States by area. It is situated in the northwest extremity of the North American continent, with Canada to the east, the Arctic Ocean to the north, and the Pacific Ocean to the west and south, with Russia further west across the Bering Strait...
, and Hawaii
Hawaii
Hawaii is the newest of the 50 U.S. states , and is the only U.S. state made up entirely of islands. It is the northernmost island group in Polynesia, occupying most of an archipelago in the central Pacific Ocean, southwest of the continental United States, southeast of Japan, and northeast of...
.
Approximately 90% of all infections occur within the months of April to September, the time period in which adult and nymphal ticks are the highest. The areas of the U.S. with the greatest reported cases of RMSF are the mid to south Atlantic states, including DE, MD, DC, VA, WV, NC, SC.
It is estimated that approximately 1200 or more new cases of RMSF will present on a yearly basis.
Clinical manifestations
The Centers for Disease Control and PreventionCenters for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
states that the diagnosis of RMSF must be made based on the clinical signs and symptoms of the patient and later confirmed using specialized laboratory tests. However, the diagnosis of RMSF is often missed due to its non-specific onset. The clinical signs and symptoms that a patient may experience could appear and may be misdiagnosed as other diseases even by the most experienced physician.
Initial signs and symptoms
During the initial stages of the disease, the patient will experience fever, nausea, vomiting, and loss of appetite.Rash
The classic RMSF rash occurs in about 90% of patients and develops 2 to 5 days after the onset of fever. The characteristic rash appear as small, flat pink macules that develop peripherally on the patient's body, such as the wrists, forearms, ankles, and feet. During the course of the disease, the rash will take on a more darkened red to purple spotted appearance and a more generalized distribution.Late signs and symptoms
Diarrhea, abdominal and joint pain, and pinpoint reddish lesions (petechiae) are observed during the late stages of the disease.Long-term implications
Patients with severe infections may require hospitalization. They may become thrombocytopenic, hyponatremic, experience elevated liver enzymes, and other more pronounced symptoms. It is not uncommon for severe cases to involve the respiratory system, central nervous system, gastrointestinal system or the renal system. This disease is worst for elderly patients, males, African-Americans, alcoholics, and patients with G6PD deficiency.Physician diagnosis
A proper physician's diagnosis is crucial during the early stages of RMSF. However, due to the fact that the signs and symptoms are very non-specific at onset, RMSF can often be misdiagnosed. For this reason, it is vital for a physician to treat the patient based on suspicion alone.Laboratory confirmation
Rocky Mountain Spotted Fever is often diagnosed using an indirect immunofluorescence assay (IFA), which is considered the reference standard by the Centers for Disease Control and PreventionCenters for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC). The IFA will detect an increase in IgG or IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
antibodies.
A more specific lab test used in diagnosing RMSF is polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
or PCR which can detect the presence of rickettiae DNA.
Immunohistochemical (IHC) staining is another diagnostic approach where a skin biopsy is taken of the spotted rash; however, sensitivity is only 70%.
Antibiotics
DoxycyclineDoxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...
and Chloramphenicol
Chloramphenicol
Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...
are the most common drugs of choice for reducing the symptoms associated with RMSF. When it is suspected that a patient may have RMSF, it is crucial that antibiotic therapy be administered promptly. Failure to receive antibiotic therapy, especially during the initial stages of the disease, may lead to end-organ failure (heart, kidney, lungs, meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...
, shock, and even death.
External links
- Rickettsia rickettsii genomes and related information at PATRIC, a Bioinformatics Resource Center funded by NIAID