Bartonella quintana
Encyclopedia
Bartonella quintana, originally known as Rochalimaea quintana, and "Rickettsia quintana", is a microorganism
Microorganism
A microorganism or microbe is a microscopic organism that comprises either a single cell , cell clusters, or no cell at all...

 that is transmitted by the human body louse. This microorganism is the caustative agent of trench fever
Trench fever
Trench fever is a moderately serious disease transmitted by body lice. It infected armies in Flanders, France, Poland, Galicia, Italy, Salonika, Macedonia, Mesopotamia, and Egypt in World War I Trench fever (also known as "Five day fever", "Quintan fever" (febris Quintana in Latin), "Urban trench...

. This bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 resulted in over 1 million soldiers in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...

 during World War I
World War I
World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...

 being infected with Trench Fever.

Background and Characteristics

Bartonella quintana is a fastidious areobicGram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

 bacteria, and it is rod-shaped or (bacillus
Bacillus
Bacillus is a genus of Gram-positive, rod-shaped bacteria and a member of the division Firmicutes. Bacillus species can be obligate aerobes or facultative anaerobes, and test positive for the enzyme catalase. Ubiquitous in nature, Bacillus includes both free-living and pathogenic species...

), in morphology
Morphology (biology)
In biology, morphology is a branch of bioscience dealing with the study of the form and structure of organisms and their specific structural features....

. The infection caused by this microorganism, trench fever, was first documented in soldiers during World War I, but has now been seen Europre, Asia and North Africa. It's primary vector is known to be "Pediculus humanus
Body louse
The body louse is a louse which infests humans. The condition of being infested with head lice, body lice, or pubic lice is known as pediculosis.-Origins:...

" variety corporis
Pediculosis corporis
Pediculosis corporis is a cutaneous condition caused by body lice that lay their eggs in the seams of clothing.- See also :* Pediculosis* Skin lesion...

, also known as the human body louse. It was first isolated in axenic
Axenic
In biology, axenic describes a culture of an organism that is entirely free of all other "contaminating" organisms. The earliest axenic cultures were of bacteria or unicellular eukaryotes, but axenic cultures of many multicellular organisms are also possible...

 culture by J.W. Vinson in 1960, from a patient in Mexico City. He then followed Koch's postulates
Koch's postulates
Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890...

, infecting volunteers with the bacteria, showing consistent symptoms and clinical manifestations of Trench Fever. The media best for growing this bacteria are blood-enriched media in an atmosphere containing 5% carbon dioxide.

Pathophysiology

Humans are the only known animal host for this bacteria in vivo
In 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...

. The bacteria infects endothelial cells and can infect erythrocytes by binding and entering with a large vacuole. Once inside they begin to proliferate and cause nuclear atypia(this is known as intraerythrocytic B.quintana colonization). This leads to apoptosis being suppressed, pro-inflammatory cytokines are released and vascular proliferation increases. All of these processes result in patients possessing systemic symptoms (chills, fever, diaphoresis), bacteremia and lymphatic enlargement. A major role in B.quintana infection is it's lipopolysaccharide (LPS) covering which is an antagonist of the Toll-like receptor 4 (TLR-4). The reason why this infection might persist is because this organism also results in monocytes over-producing interleukin-10 (IL-10), thus weakening the immune response. B.quintana also induces lesions seen in bacillary angiomatosis
Bacillary angiomatosis
Bacillary angiomatosis is a form of angiomatosis associated with bacteria of the Bartonella genus.-Causes:It is caused by either Bartonella henselae or Bartonella quintana....

 that protrude into vascular lumina, often occluding blood flow. The enhanced growth of these cells is believed to be due to the secretion of angiogenic factors, thus inducing neovascularization
Neovascularization
Neovascularization is the formation of functional microvascular networks with red blood cell perfusion. Neovascularization differs from angiogenesis in that angiogenesis is mainly characterized by the protrusion and outgrowth of capillary buds and sprouts from pre-existing blood vessels.In...

. Release of a icosahedral particle, 40 nm in length, has been detected in cultures of quintana's close relative, henselae. This particle contains a 14-kb linear DNA segment, however it's function in Bartonella pathophysiology is still unknown.
In Trench Fever or B.quintana-induced endocarditis patients, Bacillary Angiomatosis lesions are also seen. Notably, endocarditis is a new manifestation of the infection, not seen in WWI troops.

Ecology/Epidemiology

Bartonella quintana infection has subsequently been seen in every continent except Antartica. Local infections have been associated with risk factors such as poverty, alcoholism and homelessness. Serological evidence of B.quintana infection showed that of hospitalized homeless patients, 16% were infected, as opposed to 1.8% of non-hospitalized homeless persons, and 0% blood donors at large. Lice have been demonstrated, as of recently, to be the key componetent in trasmitting B.quintana, as several epidemiological studies have demonstrated.
This has been attributed to living in unsanitary conditions and crowded areas, where there is the increased risk of coming into contact with other individuals carrying B. quintana and ectoparasites (body louse). Also noteworthy, the increasing migration worldwide may also play a role in spreading Trench Fever, from area's where it is endemic to susceptible populations in urban areas. Recent concern is the possibility of the emergence of new strains of B. quintana through horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

, which could result in the acquisition of other virulence factors. This is the theory for the recent increase in prevalence of Trench Fever that has been seen.

Clinical Manifestations

The clinical manifestations of B.quintana infection are highly variable. The incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...

 is now known to be 5-20 days, as opposed to original thought which was 3-38 days. The infection can start out as an acute onset of a febrile episode, relapsing febrile episodes, or as a persistent typhoidal illness. Commonly seen are maculopapular rashes
Maculopapular rash
A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. The term "maculopapular" is a compound: macules are small, flat discolored spots on the surface of the skin; and papules are small, raised bumps...

, conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...

, headache and myalgias, with splenomegaly
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...

 being less common. Most patients present with pain in the lower legs (shins), sore muscles of the legs and back, and hyperaesthesia of the shins. Rarely is B.quintana infection fatal, unless endocarditis
Endocarditis
Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves . Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or even on intracardiac devices...

 develops and goes untreated. Weightloss, and thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...

 are sometimes also seen. Recovery can take up to a month long.

Diagnosis and Treatment

To have a definite diagnosis of infection with Bartonella quintana, requires specific tests either serological, cultures, or nucleic acid amplification techniques. To differentiate between different species, immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...

 assays that use mouse antisera are used, as well as DNA hybridization and restriction fragment length polymorphisms, or citrate synthase
Citrate synthase
The enzyme citrate synthase exists in nearly all living cells and stands as a pace-making enzyme in the first step of the Citric Acid Cycle . Citrate synthase is localized within eukaryotic cells in the mitochondrial matrix, but is encoded by nuclear DNA rather than mitochondrial...

 gene sequencing. Treatment usually consists of a 4-6 week course of doxycycline
Doxycycline
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...

, erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

 or azithromycin
Azithromycin
Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...

.
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