''Rickettsia typhi'' is a small,
aerobic, obligate intracellular, rod shaped
gram negative bacterium
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
.
It belongs to the typhus group of the ''Rickettsia'' genus, along with
''R. prowazekii''.
''R. typhi'' has an uncertain history, as it may have long gone shadowed by epidemic typhus (''R. prowazekii'').
This bacterium is recognized as a
biocontainment
One use of the concept of biocontainment is related to laboratory biosafety and pertains to microbiology laboratories in which the physical containment of pathogenic organisms or agents ( bacteria, viruses, and toxins) is required, usually ...
level 2/3 organism.
''R. typhi'' is a
flea
Flea, the common name for the order Siphonaptera, includes 2,500 species of small flightless insects that live as external parasites of mammals and birds. Fleas live by ingesting the blood of their hosts. Adult fleas grow to about long, ...
-borne disease that is best known to be the causative agent for the disease
murine typhus, which is an
endemic
Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
typhus in humans that is distributed worldwide.
As with all rickettsial organisms, ''R. typhi'' is a zoonotic agent that causes the disease ''
murine typhus'', displaying non-specific mild symptoms of fevers, headaches, pains and rashes.
There are two cycles of ''R. typhi'' transmission from animal reservoirs containing ''R. typhi'' to humans: a classic rat-flea-rat cycle that is most well studied and common, and a secondary periodomestic cycle that could involve cats, dogs, opossums, sheep, and their fleas.
''R. typhi'' was once one of the most prevalent causes of rickettsial diseases worldwide, but has since experienced a drop in case reports with the implementation of
pest control programs.
The
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
is concentrated in warmer climate and coastal ports where there is an abundance of rats and their fleas, which are the preferred hosts for the
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
.
''R. typhi '' is transmitted between competent flea and mammalian hosts through flea bites and contact with infected
feces and tissues.
There are several
laboratory
A laboratory (; ; colloquially lab) is a facility that provides controlled conditions in which scientific or technological research, experiments, and measurement may be performed. Laboratory services are provided in a variety of settings: physi ...
tests available for the
diagnosis
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...
of ''Rickettsial'' species, with the traditional diagnosis based on
serology.
However, newer laboratory techniques such as real-time
PCR and
microimmunofluorescence can be used to identify ''Rickettsia'' faster and down to the ''Rickettsia typhi''
species
In biology, a species is the basic unit of classification and a taxonomic rank of an organism, as well as a unit of biodiversity. A species is often defined as the largest group of organisms in which any two individuals of the appropriat ...
level.
History and taxonomy
In the early 20th century
epidemic
An epidemic (from Greek ἐπί ''epi'' "upon or above" and δῆμος ''demos'' "people") is the rapid spread of disease to a large number of patients among a given population within an area in a short period of time.
Epidemics of infectious ...
typhus (''R. prowazekii'') ran rampant throughout many parts of the world. It was associated with high mortality, high
virulence, and thought to be transmitted via
louse.
During this period, less severe and untraceable cases began appearing.
These cases were characterized by fever, rash, headache, as well as
musculoskeletal and gastro intestinal signs. Epidemiologist Kenneth F Maxy recognized this and began questioning and isolating the presence of another
typhus within the United States aside from ''R. prowazekii'', he detailed this in an article released in 1926.
Maxy speculated the presence of another
arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
vector transmitting this new form of typhus, which would later be discovered as ''R. typhi''.
It is thought that ''R. typhi'' has historically been under diagnosed compared to its typhus group member ''R. prowazekii''.
The discovery of ''R. typhi'' lead to the creation of the typhus group Rickettsia, which contains ''R. typhi'' and ''R. prowazekii''.
Rickettsia species are generally broken into 3 groups, the spotted fever group, typhus group and scrub typhus group.
Cellular morphology and motility
''Rickettsia typhi'' is a small,
aerobic, obligate intracellular, rod shaped,
gram negative bacterium.
''R. typhi'' is a
zoonotic bacterium that is recognized as a
biocontainment
One use of the concept of biocontainment is related to laboratory biosafety and pertains to microbiology laboratories in which the physical containment of pathogenic organisms or agents ( bacteria, viruses, and toxins) is required, usually ...
level 2/3 organism (dependent upon the tissue being worked with).
As obligate intracellular pathogens, R''. typhi'' can be difficult to isolate, and are not able to be
cultured using standard plating methods seen with most other organisms.
''R. typhi'' are
motile, creating movement through
actin based motility, with little control over directionality and speed, and are often seen moving in a circular pattern.
Virulence
''Rickettsia typhi'' is a flea-borne disease organism and is widely distributed throughout the world. There are two cycles in ''R. typhi'' transmission from animal reservoirs to human: a classic rat-flea-rat cycle, and a peridomestic cycle involving cats, dogs, opossums, sheep, and their fleas.
Classic rat-flea-rat cycle
''R. typhi'' circulates amongst rats (''
Rattus rattus'' or ''
Rattus norvegicus)'' and rat fleas (''
Xenopyslla cheopis''),
but other rodents and their
ectoparasites also play a role in maintaining ''R. typhi'' in nature.
While the rat flea is the main
vector of ''R. typhi'', ''P. h. humanus, Polypax'' lice and bloodsucking mites of rats have been reported to be capable of acquiring ''R. typhi'', either naturally or experimentally.
Transmission of ''R. typhi'' from the rat flea is affected by contact with rickettsia-containing flea feces during or after blood feeding, as well as via flea bite.
The rickettsiae have no harmful effects on the
fitness of either the vector or the rat, showing a true
mutual relationship.
Infected fleas can maintain ''R. typhi'' for life, giving them potential for infecting large number of
susceptible hosts.
Peridomestic cycle
Thus far, there have not been many studies on the periodomestic animal cycle of transmission, with the majority that have been done focusing on cats.
It has been shown that ''R. typhi'' can be present in cats and the cat flea, ''
Ctenocephalides felis,'' which is a flea species that readily bites humans. So far, there has been no direct human ''R. typhi'' infections from cats, but instead an association between high rates of infected cats related to human cases of
murine typhus in the same geographical location.
There is also some evidence that other domestic animals such as dogs and sheep,
as well as opossums,
could be involved in the ''R. typhi'' transmission cycle, but studies are currently limited.
Pathogenesis
''Rickettsia spp.'' including ''R. typhi'' enter the skin and spread through the bloodstream to infect the
endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
lining the blood vessels. This leads to vascular
inflammation
Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
, damage to vascular integrity, and compromised
vascular permeability
Vascular permeability, often in the form of capillary permeability or microvascular permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules (drugs, nutrients, water, ions) or even whole cells ( lymp ...
, which is collectively known as 'Rickettsial vasculitis'
Disease
Murine typhus (endemic typhus) in humans
''Rickettsia typhi'' is a causative agent of
murine typhus (endemic typhus) in humans and is distributed worldwide.
It is an acute,
febrile illness that is mainly transmitted by the fleas of rodents, commonly associated with cities and ports where urban rats (''
Rattus rattus'' and ''
Rattus norvegicus'') are abundant.
Humans acquire infection by inhalation or by self-inoculating infected fleas or flea feces into skin when they visit disease-
endemic
Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
areas infested with rats.
Most patients present with a fever, and many have a rash and headache,
although it can also lead to
disseminated, multisystem disease including infections of the brain, lung, liver, kidney, and heart endothelia. As these signs and
symptoms are similar to those produced by other diseases, including other rickettsiae,
murine typhus is difficult to diagnose clinically.
In addition to non-uniform and non-specific symptoms, there is a lack of
diagnostic tests
A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic t ...
effective during the acute stages of the illness, leading to delayed appropriate treatment.
Murine typhus may generally be clinically mild, but severe and even fatal cases have been reported.
The severity of
murine typhus infection has been associated with age, race, and delayed diagnosis.
Doxycycline is the antibiotic of choice as it is shown to shorten the course of illness,
although 99% of those infected will clear the disease within weeks without specific treatment.
Epidemiology
Geographical and temporal distribution
''Rickettsia typhi'' is a small,
gram-negative
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
intracellular bacterium that establishes the
murine typhus infection in mammals and fleas.
Murine typhus was once one of the most prevalent
rickettsial diseases in the world,
having isolated the ''R. typhi'' causative agent from nearly every continent around the globe except for Antarctica.
In addition to the widespread distribution, the bacterium is particularly concentrated in regions that boast warmer climates year-round and hug the coasts.
This predilection is due to these regions' favourable climatic conditions for the survival of flea and wildlife
hosts
A host is a person responsible for guests at an event or for providing hospitality during it.
Host may also refer to:
Places
* Host, Pennsylvania, a village in Berks County
People
*Jim Host (born 1937), American businessman
*Michel Host ...
, leading to their greater abundance and ability to maintain the rickettsial organism as
reservoirs in the environment.
Seaports are exceptional foci for ''R. typhi'' as infected rodents and their
ectoparasites could be introduced through the international movement of ships.
These ports can subsequently transfer the
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a g ...
to nearby cities that line the main routes of trade.
Spikes in ''R. typhi'' infections are also reported from late Spring to early Autumn when flea populations are especially high.
Historically, thousands of murine typhus cases were reported in the United States every year;
however, the disease experienced a sudden decline in incidence in the 1940s with the implementation of
pest control programs to remove the flea and rodent reservoirs responsible for rickettsial transmission in urban dwellings.
Murine typhus infections in the present are more sporadic and infrequent, with fewer than 100 cases reported in the US annually.
Nevertheless, ''R. typhi'' is still regarded as a bacterium of considerable public health significance, and outbreaks are commonly reported in the Southern US, Southern Europe, Asia, Africa, and Australia.
It is estimated that ''R. typhi'' prevalence is actually higher than the measured value, since murine typhus is often underreported and misdiagnosed because of its non-specific and mild clinical presentation (fever, headache, generalized pain, and rashes).
Undiagnosed infections are predicted to outnumber reported cases by 4:1.
A recent study presented a clinical case of a patient that works in the Brazilian Amazon and presented an unspecific febrile illness probably caused by ''Rickettsia typhi'' since the patient presented specific antibodies to this bacteria. This shows that the ''R. typhi'' geographical distribution can be wider than expected.
Host range and transmission
The ''R. typhi''
microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in old ...
obligately resides within the
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellu ...
cells of the
midgut in
flea
Flea, the common name for the order Siphonaptera, includes 2,500 species of small flightless insects that live as external parasites of mammals and birds. Fleas live by ingesting the blood of their hosts. Adult fleas grow to about long, ...
hosts, and the
endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
cells lining the
vasculature of
mammalian species.
The bacterium's lifecycle classically involves the Oriental rat flea (''
Xenopsylla cheopis'') and the black (''
Rattus rattus'') and brown (''
Rattus norvegicus'') rats.
These globally distributed hosts are especially proficient at transmitting this rickettsiae for many reasons: ''X. cheopis'' has an incredibly wide host range and can thus transmit the bacterium to a broad set of mammalian hosts, including humans;
members of the genus ''Rattus'' enable ''R. typhi'' to undergo massive rounds of
binary fission within
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells and increase the number of bacteria available to infect flea
vectors.
In addition to rats and their fleas, other hosts have been observed to naturally carry the
microparasite as well, including cats and their fleas (''
Ctenocephalides felis''), opossums, shrews, skunks, house mice and their fleas (''Leptopsylla segnis),''
and rarely dogs.
Cats and opossums are thought to be fairly significant reservoirs for murine typhus in urban environments due to their unpicky ectoparasites and close association with humans.
The bacterium transmits from an infected rat (or other mammalian host) to a susceptible rat flea (or other
arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and cuticle made of chiti ...
vector) through a blood meal, and is then transmitted from an infected flea to another susceptible rat through direct contact with the infectious feces or tissues of the vector.
Transmission through contact with arthropod feces may be through an open wound, the
respiratory tract (inhalation), or the
conjunctiva
The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithel ...
e of the mammalian host.
There is evidence that flea bite transmission is possible as well after the bacterium undergoes a certain
incubation period in the arthropod vector.
Female fleas can also pass the infection onto offspring through
transovarial transmission.
''R. typhi'' appears to be in a truly
commensal relationship with these insect and non-human hosts, as it only produces an
asymptomatic infection that has no effect on host life span or reproductivity.
Because of its versatility in transmission, the ''R. typhi'' bacterium is very successful in perpetuating its numbers in
endemic
Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found else ...
regions.
Zoonotic potential
As with all rickettsiae species, ''R. typhi'' is a
zoonotic agent with humans serving as aberrant dead-end hosts, and thus do not play an ecological role in the bacterium's transmission and lifecycle.
Humans are most commonly infected through flea and rat ''R. typhi''
carrier
Carrier may refer to:
Entertainment
* ''Carrier'' (album), a 2013 album by The Dodos
* ''Carrier'' (board game), a South Pacific World War II board game
* ''Carrier'' (TV series), a ten-part documentary miniseries that aired on PBS in April 20 ...
s in indoor environments, typically affecting individuals in occupations or living conditions that surround heavy rodent and flea populations.
The murine typhus disease is generally considered a mild affliction, with a 4%
case fatality rate in untreated patients.
Proper murine typhus oversight is especially critical in elderly patients that often require hospitalization as the disease progresses.
Diagnosis and identification
The laboratory tests available for the
diagnosis
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...
of ''Rickettsial'' species includes: shell vial assay,
PCR-based detection, immunodetection, circulating
endothelial
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the ve ...
cells, and serodiagnostic tests such as the Weil-Felix test, CF test,
ELISA
The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...
,
microimmunofluorescence, immunoperoxidase, line blot and
Western immunoblot tests.
Traditionally, the
diagnosis
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...
of ''Rickettsia'' was based on
serology However, serologic tests take about 15 days after the onset of symptoms for there to be diagnostically significant titers of ''R. tyhpi''. And so the diagnosis is often confirmed after the patient has either recovered or died.
''R. typhi'' are not able to grow in
axenic
In biology, axenic (, ) describes the state of a culture in which only a single species, variety, or strain of organism is present and entirely free of all other contaminating organisms. The earliest axenic cultures were of bacteria or unicellu ...
or sterile conditions, and must be grown in tissue, or
embryo samples.
Even when stringent physiologic conditions are met, when grown in media that mimics the environment of host
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
, pathogen activity cannot survive very long.
A common method for growing ''R. typhi'' is through the yolk sacs of embryonic eggs.
Laboratory techniques such as real-time PCR and microimmunofluorescence can be used to identify ''Rickettsia'' down to the species level.
Microimmunofluorescence is a highly sensitive test that is often used in endemic areas to confirm infection by ''R. typhi''.
The use of real-time PCR can allow for the detection and confirmation of R. typhi earlier than serological tests.
Membrane protein ompB and prsA
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
fragments have been shown to be identifiable markers in qPCR for ''R. typhi.''
Differentiation from ''R. prowazekii''
Symptoms of ''R. typhi'' and ''R. prowazekii'' can be very similar, with ''R. typhi'' infections usually being less severe. ''R. typhi'' and its typhus group member ''R. prowazekii'' are composed of very similar
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ...
s, ''R. typhi'' can be differentiated from ''R. prowazekii'' by 12000
base pairs inserted into ''R. prowazekii.''
There are various methods to differentiate among the typhus group members. One method is through restriction fragment length polymorphism (RFLP), which can differentiate the two species based on the ompB gene and associated
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s, which has a unique sequence for each species.
Serological methods are also useful. It has been shown that utilizing indirect fluorescent
antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...
assays and western blot analysis together provide reliable differentiation among the species.
Serum cross-adsorbent analysis alone is also a reliable method for differentiation, as cross reaction between the two species is common.
Bibliography
References
{{Taxonbar, from=Q3010410
Rickettsiaceae