Materiały źródłowe

• #1 Typhus: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/231374-overview

  Epidemic typhus is the prototypical infection of the flea-borne rickettsioses group of diseases, and the pathophysiology of this illness is representative of the entire category. The arthropod vector of epidemic typhus is the body louse (Pediculus humanus humanus). This is the only vector of the group in which humans are the usual host. Rickettsia prowazekii, which is the etiologic agent of epidemic typhus, lives in the alimentary tract of the louse. A Rickettsia-harboring louse bites a human to engage in a blood meal and causes a pruritic reaction on the host’s skin. The louse defecates as it eats; when the host scratches the site, the lice are crushed, and the Rickettsia-laden excrement is inoculated into the bite wound. The Rickettsia travel to the bloodstream and rickettsemia develops.

• #2 Epidemic typhus – UpToDate

  https://www.uptodate.com/contents/epidemic-typhus/print

  Epidemic typhus is a potentially lethal, louse-borne, exanthematous disease caused by Rickettsia prowazekii. R. prowazekii is one of two members of the typhus group of Rickettsia known to cause human illness; the other member, Rickettsia typhi, causes murine typhus. […] The epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of epidemic typhus will be discussed here. […] Epidemic typhus is now a rare disease, but subsequent developments illustrate that an understanding of its epidemiology, clinical features, and treatment is still important to clinicians.

• #3 Clinical Overview of Epidemic Typhus | Typhus Fevers | CDC

  https://www.cdc.gov/typhus/hcp/clinical-overview/clinical-overview-of-epidemic-typhus.html

  The primary vector of epidemic typhus is Pediculus humanus corporis (human body louse). People become infected with Rickettsia prowazekii when they come into contact with the feces or crushed bodies of infected lice on cut or abraded skin. […] R. prowazekii can remain infective in louse feces for up to 100 days. […] Delay in treatment with doxycycline may lead to progression of the disease, including neurologic manifestations such as confusion, seizures, or coma, and widespread vasculitis. These symptoms are due to damage to the vascular endothelial cells throughout small blood vessels. […] R. prowazekii can be detected via indirect fluorescent antibody (IFA) test, immunohistochemistry (IHC), polymerase chain reaction (PCR) assay of blood, plasma, or tissue samples, or culture isolation. […] Doxycycline is the treatment of choice for suspected cases of acute epidemic typhus and Brill-Zinsser disease in adults and children of all ages.

• #4 Scrub Typhus- Etiology, Epidemiology, Symptoms, Pathogenesis, Diagnosis and Treatment

  https://microbiologyinfo.com/scrub-typhus-etiology-epidemiology-symptoms-pathogenesis-diagnosis-and-treatment/

  Endothelial cells of most organs including skin, heart, lung, brain, kidney, pancreas, have been presented as the target cells of O. tsutsugamushi. […] The bacteria multiply at the inoculation site, and a papule forms that ulcerates and becomes necrotic, evolving into an eschar, with regional lymphadenopathy that may progress to generalized lymphadenopathy within a few days. […] O. tsutsugamushi stimulates phagocytosis by the immune cells, and then escapes the phagosome. […] It replicates in the cytoplasm and then buds from the cell. […] The bacteria are able to harness the microtubule assembly inside the human cell for movement. […] Scrub typhus may disseminate into multiple organs through endothelial cells and macrophages, resulting in the development of fatal complications. […] One study conducted in adult Thai patients have suggested that Orientia tsutsugamushi induces a type 1 immune response, associated with elevation of interferonalpha, IL-18 and IL-15 levels.

• #5 A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow

  https://www.mdpi.com/2414-6366/3/1/8

  Scrub typhus and the rickettsial diseases represent some of the oldest recognized vector-transmitted diseases, fraught with a rich historical aspect, particularly as applied to military/wartime situations. […] Orientia tsutsugamushi is an obligate, intracellular bacterium and the causative agent of scrub typhus disease in humans. […] The agents of the order Rickettsiales (both of known and unknown pathogenicity) are potentially transmitted to humans via the biting and/or contamination of mucous membranes/lesions by ectoparasites/arthropods such as hard or soft ticks, fleas, mosquitoes, mites, lice, and fleas. […] Specifically, O. tsutsugamushi is vectored by the biting of the larval life stage of infected Leptotrombidium mites. […] While it was previously thought by some researchers that vertebrate hosts, especially mammals, may serve as reservoirs, it is now accepted that trombiculid mites are both the vector and reservoir for O. tsutsugamushi.

• #6 Typhus: Causes, Symptoms, and Diagnosis

  https://www.healthline.com/health/typhus

  Typhus is a disease caused by infection with one or more rickettsial bacteria. Fleas, mites (chiggers), lice, or ticks transmit it when they bite you. […] When arthropods carrying around rickettsial bacteria bite someone, they transmit the bacteria that causes typhus. Scratching the bite further opens the skin and allows the bacteria greater access to the bloodstream. Once in the bloodstream, the bacteria continue to reproduce and grow. […] The louse, flea, tick, or mite becomes a carrier of the bacteria when they feed on the blood of an infected person (epidemic typhus) or an infected rodent (any of the three typhus forms mentioned above). […] If you come in contact with these bacterium-carrying arthropods (for example, by sleeping on bed sheets infested with lice), you can become infected in a couple ways. The bacteria, in addition to being transmitted through your skin by their bites, can also be transmitted through their feces. If you scratch the skin over an area where lice or mites have been feeding, the bacteria in their feces can enter your bloodstream through the tiny wounds on your skin.

• #7 Murine Typhus

  https://www.redalyc.org/journal/283/28323195011/html/

  Rickettsial pathogeny depends of intracythoplasmatic niche rich in nutrients and grows requirements inside the cell host. Invasion to cell is an essential previous requirement for intracellular replication and after all intracellular diffusion. […] Endothelial injury is the key element in the pathogenic and pathophysiology of endemic typhus. R. typhi adheres to endothelial cells through outer membrane proteins. Among the major outer membrane surface proteins are OmpA and OmpB which are present in the Rickettsial Spotted Fever Group and the Transition Group, while the Typhus Group Rickettsia only have OmpB and his cellular receptor still unknown. […] Immediately to his adhesion, R. typhi penetrate endothelial cells by phagocytosis induced by the pathogen. Rickettsial invasion requires the presence of cholesterol-rich microdomains containing Ku70 and the ubiquitin ligase, c-CBL, the input focus to the ubiquitination of Ku70. […] Once inside, spreads to nearby cells by a peculiar mechanism involving rearrangement of actin and endothelial cell production of direct endothelial injury in which free oxygen radicals are involved.

• #8 Murine Typhus: Clinical and epidemiological aspects

  http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S1657-95342012000200011

  Rickettsial pathogeny depends of intracythoplasmatic niche rich in nutrients and grows requirements inside the cell host. Invasion to cell is an essential previous requirement for intracellular replication and afterall intracellular diffusion. […] Endothelial injury is the key element in the pathogenic and pathophysiology of endemic typhus. R. typhi adheres to endothelial cells through outer membrane proteins. Among the major outer membrane surface proteins are OmpA and OmpB which are present in the Rickettsial Spotted Fever Group and the Transition Group, while the Typhus Group Rickettsia only have OmpB and his cellular receptor still unknown. […] Rickettsial invasion requires the presence of cholesterol-rich microdomains containing Ku70 and the ubiquitin ligase, c-CBL, the input focus to the ubiquitination of Ku70.

• #9 Murine Typhus: Clinical and epidemiological aspects

  http://www.scielo.org.co/scielo.php?script=sci_arttext&pid=S1657-95342012000200011

  Recent research with electron microscopy indicate that the entry of Rickettsia in mammalian cells occurs within minutes after contact, this interaction, therefore, is almost instantaneous and once internalized, Rickettsia is able to escape quickly in the cytoplasm, probably before fusion phage – lisosoma and is suspected is done through a phospholipase activity. […] Once inside, spreads to nearby cells by a peculiar mechanism involving rearrangement of actin and endothelial cell production of direct endothelial injury in which free oxigen radicals are involved.

• #10 Scrub Typhus Diagnostics: The Present and the Future – ScienceOpen

  https://www.scienceopen.com/hosted-document?doi=10.15212/ZOONOSES-2023-0028

  The organism has a predilection for endothelial cells, dendritic cells, monocytes, and macrophages. […] At the bite site, O. tsutsugamushi attaches to the host cell and is internalized, in a process facilitated by Sca C (a bacterial autotransporter protein); the TSA 56 antigen present on the organism; and syndecan 4 (a cell surface heparan sulfate proteoglycan), fibronectin, and integrin α5β1 on the host cells. Once inside the cell, the organism is transported to the perinuclear area through dynein mediated transport on microtubules, then subsequently multiplies through binary fission. The organism is then released from the host cell through budding and begins to infect adjacent cells.

• #11 Typhus Fever: Characteristics and Lab Diagnosis • Microbe Online

  https://microbeonline.com/typhus-fever/

  Human is an accidental host in many cases and disease is prevalent in wild animals. […] Passed between animals and from animals to humans by insect vectors […] In most cases, humans become infected by the bite of infected arthropod vectors. […] Arthropod vectors deposit the organism in the bloodstream. […] Endothelial cells in the bloodstream engulf these organisms (induced by the organism itself) and are carried to the cell cytoplasm within a vacuole. […] Organisms escape from the vacuole or phagosome. […] Multiplication of the organisms- which causes cell injury and cell deaths manifested as vascular lesions which disseminated throughout the body. […] Skin, heart, brain, lungs, and muscles are primarily affected. […] Organisms transmit inside the body via cell-to-cell spread, lymphatic drainage, and hematogenous route, and can also be latent (e.g. R. prowazekii). […] Formation of disseminated endothelial lesions. […] Activation of clotting systems-disseminated intravascular coagulopathy (DIC). […] Death is usually by cardiac failure.

• #12 Typhus pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Typhus_pathophysiology

  The pathophysiology of typhus fever can be described in the following steps: […] The major pathology is caused by a vasculitis and its complications. On transmission, Rickettsia is actively phagocytosed by the endothelial cells of the small venous, arterial, and capillary vessels. It is followed by systemic hematogenous spread resulting in multiple localizing vasculitis. This process may cause result in occlusion of blood vessels and initiates inflammatory response (aggregation of leukocytes, macrophages, and platelets) resulting in small nodules. Occlusion of supplying blood vessels may cause gangrene of the distal portions of the extremities, nose, ear lobes, and genitalia. This vasculitic process causes destruction of the endothelial cells and leakage of the blood leading to volume depletion with subsequent hypovolemia and decreased tissue perfusion and, possibly, organ failure. Endothelial damage also leads to activation of clotting system (DIC).

• #13 Typhus – almostadoctor

  https://almostadoctor.co.uk/encyclopedia/typhus

  Widespread vasculitis and endothelial proliferation may affect any organ […] Thrombotic occlusion may lead to gangrene.

• #14 Typhus Clinical Presentation: History, Physical, Causes

  https://emedicine.medscape.com/article/231374-clinical

  Signs, symptoms, and potential complications of typhus are due to hematogenous spread of organisms with resultant endothelial proliferation and vasculitis. The central nervous, musculoskeletal, and cardiovascular systems may be involved, as well as the skin, lungs, and kidneys. Multiorgan system involvement is possible. […] Vasculitis may result in hypovolemia, electrolyte disturbances, and digital gangrene.

• #15 Typhus pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Typhus_pathophysiology

  Tumor necrosis factor (TNF-) produce on activation of cell mediated immunity, stimulates T lymphocytes and macrophages, which help in eliminating intracellular rickettsia. Virulent rickettsia tend to suppress the activity of tumor necrosis factor (TNF-) and IFN-gamma. Cytokines such as interleukin (IL) 12 promote production of Interferon (IFN-) responses. IFN-, which drives TH1-type responses and stimulates macrophage activation. Cytokines, which include , IL-6, IL-4and IL-10, down-regulate the protective response.

• #16 Establishment of a Novel Endothelial Target Mouse Model of a Typhus Group Rickettsiosis: Evidence for Critical Roles for Gamma Interferon and CD8 T Lymphocytes | Laboratory Investigation

  https://www.nature.com/articles/3780144

  A mouse model of typhus rickettsiosis that reproduces the hematogenous dissemination to the critical target organs, including brain, lungs, heart, and kidneys, primary endothelial and, to a lesser degree, macrophage intracellular rickettsial infection, and typical vascular-based lesions of louse-borne typhus and murine typhus was established. […] Gamma interferon and CD8 T lymphocytes were demonstrated to be crucial to clearance of the rickettsiae and recovery from infection in experiments in which specific monoclonal antibodies were administered to deplete these components. […] This model offers excellent opportunities for study of attenuation and pathogenetic mechanisms of typhus rickettsiae, which are established biologic weapons of potential use in bioterrorism. […] Research on the pathogenesis of typhus and the mechanisms of immunity to typhus group rickettsiae has been constrained by the lack of a reproducible animal model in which the endothelial cell is the major target and the vascular pathology resembles the human typhus fevers.

• #17 Scrub Typhus- Etiology, Epidemiology, Symptoms, Pathogenesis, Diagnosis and Treatment

  https://microbiologyinfo.com/scrub-typhus-etiology-epidemiology-symptoms-pathogenesis-diagnosis-and-treatment/

  During the initial inflammatory response to infections, early response cytokines (tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6) up-regulate cellular adhesion molecules (CAMs) on the surface of host leucocytes and endothelial cells (EC), which co-ordinate leucocyte transmigration across the endothelium. […] The selectins mediate initial leucocyte contact with EC, capturing cells from the bloodstream, followed by characteristic rolling and firm tethering to the endothelium. This requires higher-affinity leucocyte integrins (LFA-1 and Mac-1) binding to members of the immunoglobulin (Ig) superfamily, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1), which are expressed on activated EC, enabling subsequent leucocyte diapedesis.

• #18 Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008675

  In SFR, microglial expansion and macrophage infiltration contribute to neurological disease progression. […] The etiological agent of scrub typhus, Orientia tsutsugamushi, is transmitted via the bite of the Leptotrombidium mite (chigger) and remains endemic to a region spanning most of Asia to Northern Australia, termed the tsutsugamushi triangle. […] O. tsutsugamushi is an obligately intracellular bacterium that targets endothelial cells and phagocytes for replication. […] Accordingly, disease pathogenesis predominates in highly vascularized organs (lung, liver, brain, etc.), manifesting as interstitial pneumonia, liver damage, and meningoencephalitis. […] If left untreated, scrub typhus may lead to multiorgan failure, with fatality rates ranging from 0% to 70%, with a median of 6%.

• #19 Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008675

  Neurological manifestations and sequelae of scrub typhus and SFR have been overlooked. […] Yet, little is known about the pathogenesis associated with Orientia and Rickettsia infections, and even less is known about neuroinflammation associated with these infections. […] Here, we compare clinical symptoms, signs, and sequelae of SFR and scrub typhus as well as the molecular pathogenesis of both diseases, highlighting new evidence from related mouse models. […] Scrub typhus severity is dependent on host immune status and the O. tsutsugamushi strains involved; the Karp serotype (OtK) is the most prevalent strain in patients, accounting for approximately 40% of infections in endemic countries. […] In 2014, Keller and colleagues used inbred BALB/c mice and provided evidence for dissemination of OtK from footpad inoculation site to draining lymph nodes and visceral organs (lungs, brain, etc.).

• #20 Scrub Typhus Pathogenesis: Innate Immune Response and Lung Injury During Orientia tsutsugamushi Infection

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6742975/

  Damage to the vasculature promotes the production of proinflammatory cytokines (i.e., CXCL8 and TNF) leading to recruitment of leukocytes, especially neutrophils, which secrete their own chemokines and effector proteins, inducing a proinflammatory microenvironment. […] In scrub typhus, about 644% of cases develop ARDS. […] Certain risk factors appear to be important for ARDS development during scrub typhus: septic shock, hypoalbuminemia, high circulating white blood cell counts, delayed antibiotic treatment, and advanced age. […] Lung infection is common during scrub typhus, and patients typically develop mild interstitial pneumonitis during self-resolving or promptly treated scrub typhus. […] However, in severe cases, pulmonary pathology includes lung hemorrhage, pulmonary edema, vasculature damage, and diffuse cellular infiltration resulting in ARDS.

• #21 Scrub typhus: Overview, Pathogenesis and Lab Diagnosis • Microbe Online

  https://microbeonline.com/scrub-typhus-overview-pathogenesis-and-lab-diagnosis/

  Human infection is initiated via the bite of an infected larval Leptotrombidium mite (also known as a chigger). The incubation period ranges from 6 to 21 days (usually, 10-12 days). Disease onset is characterized by fever, headache, myalgia, cough, and gastrointestinal symptoms. The severity of the symptoms varies widely, depending on the susceptibility of the host, the virulence of the bacterial strain, or both. […] From the second week of onset, if untreated, patients show evidence of systemic infection. This stage of illness can attack different organ systems such as the central nervous system (acute diffuse encephalomyelitis, encephalopathy, meningitis, deafness, cranial nerve palsies, eye manifestations) cardiovascular system (rhythm abnormalities, myocardial involvement with congestive heart failure, vasculitis), renal system (acute renal failure), respiratory system (Interstitial pneumonia and acute respiratory distress syndrome) and gastrointestinal system (alterations in liver functions, pancreatitis, diarrhea). Sometimes multiorgan dysfunction syndrome (MODS) occurs with an increased case-fatality if not treated promptly.

• #22 Typhus: Causes, Symptoms, and Diagnosis

  https://www.healthline.com/health/typhus

  Early treatment with antibiotics is very effective, and relapses aren’t common if you take the full course of antibiotics. Delayed treatment and misdiagnosis can lead to a more severe case of typhus. […] The overall mortality rate for untreated typhus depends on the type of typhus and other factors, such as age and overall health status. […] Mortality for epidemic typhus that goes untreated can range from 10 to 60 percent, and mortality from untreated scrub typhus can range up to 30 percent. […] Endemic/murine typhus is rarely deadly, even without treatment. Death occurs in no more than 4 percent of cases, according to an article in Clinical Infectious Diseases.

• #23 Neuroinflammation associated with scrub typhus and spotted fever group rickettsioses | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008675

  Scrub typhus and spotted fever rickettsioses (SFR) are understudied, vector-borne diseases of global significance. […] While highly treatable, diagnostic challenges make timely antibiotic intervention difficult for these diseases. Delayed therapy may lead to severe outcomes affecting multiple organs, including the central nervous system (CNS), where infection and associated neuroinflammation may be lethal or lead to lasting sequelae. […] Despite the increasing number of clinical reports outlining neurologic consequences of these diseases, relatively little research has examined underlying mechanisms of neuroinflammation. […] Animal models of scrub typhus have identified cerebral T-cell infiltration and vascular damage associated with endothelial infection and neuropathogenesis. […] Differential gene expression analysis of brain tissues during murine scrub typhus have revealed selective increases in CXCR3 ligands, proinflammatory and type-1 cytokines and chemokines, and cytotoxicity molecules, as well as alterations in the complement pathway.

• #24

  https://journals.lww.com/annalsofian/fulltext/2021/24060/neurological_facets_of_scrub_typhus__a.3.aspx

  Scrub typhus is one of the most frequent causes of acute febrile illness in South and South-east Asian countries. […] Multiple mechanisms underlie neurological involvement, including direct invasion (meningitis, encephalitis), vasculitis (myositis) or immune-mediated mechanisms (opsoclonus, myoclonus, optic neuritis, Guillain-Barre syndrome). […] The pathogenesis underlying neurological manifestations may be a combination of vasculitis or other immune phenomena triggered by the infection. […] Entry in to the CNS is via invasion of endothelial cells by O. tsutsugamushi. Endothelial cells are the primary cellular target. Subsequent endothelial cell activation leads to leukocyte adhesion and transmigration, platelet aggregation and cytokine release. […] In the CNS, resultant vasculitis leads to a plethora of complications. Direct invasion of the CSF has been reported in some studies, leading to meningitis and meningo-encephalitis. […] A third mechanism underlying neurological features is immune-mediated, due to type 2 hypersensitivity reaction targeting self-antigens. This explains certain late-onset manifestations such as opsoclonus, myoclonus, GBS and myelitis.

• #25 Opsoclonus-Myoclonus Syndrome as a Heralding Feature of Scrub Typhus: An Illustrative Case with a Video Vignette

  https://www.e-jmd.org/journal/view.php?number=340

  Dear Editor, Scrub typhus, a rickettsial illness caused by Orientia tsutsugamushi, is transmitted by the bite of the larval form (chigger) of the trombiculid mite. […] The underlying pathogenetic mechanism of OMS in scrub typhus is thought to be immune mediated, led by type 2 hypersensitivity against self-antigens due to the usual lag between fever onset and OMS onset. […] However, the exact pathogenesis of the disorder is far from clear. […] This temporal course may differentiate postinfectious syndrome from parainfectious syndrome. […] Parainfectious OMS in scrub typhus is usually transient and may resolve spontaneously. […] This case report highlights the increasingly variable and complex neurological presentation of scrub typhus. OMS is typically a well-characterized paraneoplastic syndrome with a likely antibody-mediated mechanism.

• #26 Typhus: Background, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/231374-overview

  Rickettsia sp parasitize the endothelial cells of the small vessels and proliferate, causing endothelial damage, leading to increased vascular permeability, thrombosis, and inflammation. Finally, hypovolemia, organ failure, and on occasions, death, result. […] Some people with a history of epidemic typhus may develop a recrudescent type of epidemic typhus known as Brill-Zinsser disease. After a patient with typhus is treated with antibiotics and the disease appears to be cured, Rickettsia may linger in the body tissues. Months, years, or even decades after treatment, organisms may reemerge and cause a recurrence of typhus. How the Rickettsia organisms linger silently in a person and by what mechanism recrudescence is mediated are unknown. […] Murine typhus and scrub typhus have the same physiopathology as epidemic typhus, however murine typhus usually is milder. Scrub typhus severity usually depends on time to start antibiotics, and number of recurrences. It is more severe after the first episode.

• #27 Inactivation of SAM-Methyltransferase is the Mechanism of Attenuation of a Historic Louse Borne Typhus Vaccine Strain | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113285

  Louse borne typhus (also called epidemic typhus) was one of man’s major scourges, and epidemics of the disease can be reignited when social, economic, or political systems are disrupted. […] The mechanism of the mutation in R. prowazekii that affects the virulence of the vaccine was not known. […] We concluded that a single nucleotide insertion in the methyltransferase gene of R. prowazekii attenuated the R. prowazekii vaccine strain E. […] The important question is whether smt is the only gene difference between E strain and Evir strain that causes the reversion of avirulent E strain to virulent Evir strain. […] We sequenced the genome of R. prowazekii strain Evir and compared it with the genome sequence of strain E (DOW) in GenBank and identified 31 insertions, deletions and SNPs between Evir and E strain (DOW).

• #28 Inactivation of SAM-Methyltransferase is the Mechanism of Attenuation of a Historic Louse Borne Typhus Vaccine Strain | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0113285

  The mutation interrupted smt into two open reading frames, which was designated as rp027 and rp028 previously. […] We reasoned that the reverse mutation in smt determined the virulence of R. prowazekii. […] As smt encodes a methyltransferase, these results clearly indicate that the methyltransferase gene is critical for the virulence of R. prowazekii and the attenuation of E strain might be caused by inactivation of SAM-methyltransferase. […] We concluded that a single nucleotide insertion in the methyltransferase gene smt attenuates R. prowazekii vaccine strain E, and a reversion mutation makes the revertant strain Evir.

• #29 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1022253

  The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. […] All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus. […] In this study, we determined that all DNA samples of the Boryong strain of O. tsutsugamushi contained the Ser83Leu mutation in the QRDR domain, which is known to be associated with quinolone resistance. […] However, recent studies suggest that quinolone can cause deleterious effects on Rickettsia conorii-infected cells via a mechanism linked to toxin-antitoxin module up-regulation.

• #30 KoreaMed Synapse

  https://synapse.koreamed.org/articles/1022253

  This study has several limitations. First, ciprofloxacin was administered to only one patient in this study and thus we could not evaluate the outcome of patients treated with quinolone. […] For this reason, we sequenced the gyrA gene of 20 O. tsutsugamushi Boryong samples and determined that all had the Ser83Leu mutation in their QRDR domain, suggesting intrinsic resistance to quinolone. […] In conclusion, we report the presence of the Ser83Leu mutation in gyrA samples of the Boryong strain of O. tsutsugamushi from 20 patients, suggesting that quinolone may be avoided for the treatment of scrub typhus, particularly in severe cases.

• #31 A Review of Scrub Typhus (Orientia tsutsugamushi and Related Organisms): Then, Now, and Tomorrow

  https://www.mdpi.com/2414-6366/3/1/8

  The emergence of antibiotic-resistant strains of O. tsutsugamushi is of current/future concern. […] It is known that O. tsutsugamushi is responsible for approximately one million cases of scrub typhus each year within endemic areas, and that an estimated one billion people per year are at risk of becoming infected. […] The purpose of this review is to provide an overview of the large historical impact of O. tsutsugamushi, with particular relevance to military operations; to describe the recent outbreaks of scrub typhus both within and beyond the Tsutsugamushi Triangle; to detail the information currently associated with antibiotic resistance to O. tsutsugamushi; and to summarize the current status of Orientia spp. genomics. […] The continued pursuit of diagnostic tools, enhanced therapeutics, and ultimately a broadly protective vaccine, will all be key to the reduction of the global disease burden associated with O. tsutsugamushi and other Orientia species. […] Researchers around the globe maintain the same goal of pursuing research geared towards better defining the pathogenesis of O. tsutsugamushi and its relation/translation to human scrub typhus cases.

• #32 :: Immune Network ::

  https://immunenetwork.org/DOIx.php?id=10.4110/in.2021.21.e14

  Scrub typhus develops after the individual is bitten by a trombiculid mite infected with Orientia tsutsugamushi. […] The i.n. vaccination with OMPOT induced IgG responses in serum and bronchoalveolar lavage (BAL) fluid. […] The vaccination induced strong Ag-specific Th1 and Th17 responses in the both spleen and lungs. […] The outer membrane protein of O. tsutsugamushi (OMPOT), one of the major Ags, has been used as a vaccine candidate and diagnostic target molecule. […] Therefore, we hypothesized that i.n. vaccination with OMPOT will elicit vaccine-induced immune responses by blocking O. tsutsugamushi dissemination into the lungs and inhibiting pneumonia and systemic infection by scrub typhus. […] Our study aimed to investigate the effect of OMPOT vaccination through i.n. route on the protection against O. tsutsugamushi in both mucosal and systemic compartments.

• #33 :: Immune Network ::

  https://immunenetwork.org/DOIx.php?id=10.4110/in.2021.21.e14

  Our results strongly advocate the development of a mucosal vaccine against scrub typhus that would target outer-membrane protein Ags, including OMPOT, on the surface of O. tsutsugamushi. […] Overall, our study suggested that i.n. vaccination strategy using OMPOT could provide an effective protection against scrub typhus.

• #34 Typhus pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Typhus_pathophysiology

  Typhus is a zoonotic disease, humans are infected by the bites from parasites such as fleas, lice, mites, and ticks or by the inoculation of infectious fluids or feces from the parasites into the skin. The incubation period of typhus fever varies from one to two weeks. Following transmission, rickettsia are ingested by macrophages and polymorphonuclear cells. The major pathology is caused by a vasculitis and its complications. This process may cause result in occlusion of blood vessels and initiates inflammatory response (aggregation of leukocytes, macrophages, and platelets) resulting in small nodules. This vasculitic process causes destruction of the endothelial cells and leakage of the blood leading to volume depletion with subsequent hypovolemia and decreased tissue perfusion and, possibly organ failure.

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