Review

Authors: Lucas S Blanton

Rickettsia are small, obligately intracellular, gram-negative bacilli. They are distributed among a variety of hematophagous arthropod vectors and cause illness throughout the world. Rickettsioses present as an acute undifferentiated febrile illness and are often accompanied by headache, myalgias, and malaise. Cutaneous manifestations include rash and eschar, which both occur at varying incidence depending on the infecting species. Serology is the mainstay of diagnosis, and the indirect immunofluorescence assay is the test of choice. Reactive antibodies are seldom present during early illness, so testing should be performed on both acute-phase and convalescent-phase sera. Doxycycline is the treatment of choice.

Topics: Animals; Anti-Bacterial Agents; Arthropod Vectors; Doxycycline; Humans; Rickettsia Infections; Rocky Mountain Spotted Fever

PubMed: 30712763
DOI: 10.1016/j.idc.2018.10.010

Review

Authors: Aránzazu Portillo, Sonia Santibáñez, Lara García-Álvarez...

Bacteria of the genera Rickettsia and Orientia (family rickettsiaceae, order rickettsiales) cause rickettsioses worldwide, and are transmitted by lice, fleas, ticks and mites. In Europe, only Rickettsia spp. cause rickettsioses. With improvement of hygiene, the risk of louse-borne rickettsiosis (epidemic typhus) is low in Europe. Nevertheless, recrudescent form of Rickettsia prowazekii infection persists. There could be an epidemic typhus outbreak if a body lice epidemic occurs under unfavorable sanitary conditions. In Europe, endemic typhus or Rickettsia typhi infection, transmitted by rats and fleas, causes febrile illness. At the beginning of this century, flea-borne spotted fever cases caused by Rickettsia felis were diagnosed. Flea-borne rickettsiosis should be suspected after flea bites if fever, with or without rash, is developed. Tick-borne rickettsioses are the main source of rickettsia infections in Europe. Apart from Rickettsia conorii, the Mediterranean Spotted Fever (MSF) agent, other Rickettsia spp. cause MSF-like: Rickettsia helvetica, Rickettsia monacensis, Rickettsia massiliae or Rickettsia aeschlimannii. In the 1990s, two 'new' rickettsioses were diagnosed: Lymphangitis Associated Rickettsiosis (LAR) caused by Rickettsia sibirica mongolitimonae, and Tick-Borne Lymphadenopathy/Dermacentor-Borne-Necrosis-Erythema-Lymphadenopathy/Scalp Eschar Neck Lymphadenopathy (TIBOLA/DEBONEL/SENLAT), caused by Rickettsia slovaca, Candidatus Rickettsia rioja and Rickettsia raoultii. Lastly, European reports about mite-borne rickettsiosis are scarce.

Topics: Animals; Arthropods; Europe; Humans; Orientia tsutsugamushi; Rickettsia; Rickettsia Infections; Scrub Typhus

PubMed: 26384814
DOI: 10.1016/j.micinf.2015.09.009

Authors: Luc H Boudreau, Anne-Claire Duchez, Nathalie Cloutier...

Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile nonhemolytic reactions, skin manifestations, and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospholipids, fatty acids, and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses.

Topics: Animals; Blood Platelets; DNA, Mitochondrial; Endothelium, Vascular; Flow Cytometry; Group II Phospholipases A2; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Mitochondria; Platelet Activation; Rickettsia prowazekii

PubMed: 25082876
DOI: 10.1182/blood-2014-05-573543

Authors: Casey L C Schroeder, Hema P Narra, Abha Sahni...

Emerging evidence implicates a critically important role for bacterial small RNAs (sRNAs) as post-transcriptional regulators of physiology, metabolism, stress/adaptive responses, and virulence, but the roles of sRNAs in pathogenic Rickettsia species remain poorly understood. Here, we report on the identification of both novel and well-known bacterial sRNAs in Rickettsia prowazekii, known to cause epidemic typhus in humans. RNA sequencing of human microvascular endothelial cells (HMECs), the preferred targets during human rickettsioses, infected with R. prowazekii revealed the presence of 35 trans-acting and 23 cis-acting sRNAs, respectively. Of these, expression of two trans-acting (Rp_sR17 and Rp_sR60) and one cis-acting (Rp_sR47) novel sRNAs and four well-characterized bacterial sRNAs (RNaseP_bact_a, α-tmRNA, 4.5S RNA, 6S RNA) was further confirmed by Northern blot or RT-PCR analyses. The transcriptional start sites of five novel rickettsial sRNAs and 6S RNA were next determined using 5' RLM-RACE yielding evidence for their independent biogenesis in R. prowazekii. Finally, computational approaches were employed to determine the secondary structures and potential mRNA targets of novel sRNAs. Together, these results establish the presence and expression of sRNAs in R. prowazekii during host cell infection and suggest potential functional roles for these important post-transcriptional regulators in rickettsial biology and pathogenesis.

PubMed: 27375581
DOI: 10.3389/fmicb.2016.00859

Review

Authors: Yuan-Ping Deng, Yi-Tian Fu, Chaoqun Yao...

Human lice have always been a major public health concern due to their vector capacity for louse-borne infectious diseases, like trench fever, louse-borne relapsing fever, and epidemic fever, which are caused by Bartonella quintana, Borrelia recurrentis, and Rickettsia prowazekii, respectively. Those diseases are currently re-emerging in the regions of poor hygiene, social poverty, or wars with life-threatening consequences. These louse-borne diseases have also caused outbreaks among populations in jails and refugee camps. In addition, antibodies and DNAs to those pathogens have been steadily detected in homeless populations. Importantly, more bacterial pathogens have been detected in human lice, and some have been transmitted by human lice in laboratories. Here, we provide a comprehensive review and update on louse-borne infectious diseases/bacterial pathogens.

Topics: Animals; Humans; Typhus, Epidemic Louse-Borne; Relapsing Fever; Pediculus; Phthiraptera; Communicable Diseases

PubMed: 37567429
DOI: 10.1016/j.tmaid.2023.102630

Review

Authors: C Sergio E Bermúdez, Adriana Troyo

In this paper, we present a historical review of rickettsiosis in Central America and also the most recent findings of in ectoparasites. All countries of Central America have records of rickettsiosis. Regarding the typhus group rickettsioses, there is clinical or serological evidence of in Guatemala, in Panama, Guatemala, and Costa Rica and unidentified species of the typhus group in El Salvador. Concerning spotted fever group rickettsiosis, there is serological evidence of infection by in Costa Rica and confirmed cases involving in Panama and Costa Rica. There are also reports of spotted fever group rickettsiosis in acute patients from Guatemala, Honduras, and Nicaragua. Serological studies in Central America show reactivity of , , , , and in domestic and wild mammals. Eight species of have been detected in ectoparasites from Central America: (or very similar), , , , , , , and , in addition to undescribed strains such as Atlantic Rainforest, Colombianensi, IbR/CRC, Barva, Aragaoi, and "Rickettsia nicoyana;" the latter being the only one associated with Argasidae (). is the most common species in Central America, seeing as it has been reported in 10 species of ticks and one of fleas in five of the seven countries of the region. In this study, we demonstrate that the genus is widely distributed in Central America and that rickettsiosis could be an underestimated problem in the absence of greater diagnostic efforts in undetermined febrile cases.

PubMed: 30050361
DOI: 10.2147/RRTM.S160951

Review

Authors: Ana Luísa Matos, Pedro Curto, Isaura Simões...

The order Rickettsiales includes species that cause a range of human diseases such as human granulocytic anaplasmosis (), human monocytic ehrlichiosis (), scrub typhus (), epidemic typhus (), murine typhus (), Mediterranean spotted fever (), or Rocky Mountain spotted fever (). These diseases are gaining a new momentum given their resurgence patterns and geographical expansion due to the overall rise in temperature and other human-induced pressure, thereby remaining a major public health concern. As obligate intracellular bacteria, Rickettsiales are characterized by their small genome sizes due to reductive evolution. Many pathogens employ moonlighting/multitasking proteins as virulence factors to interfere with multiple cellular processes, in different compartments, at different times during infection, augmenting their virulence. The utilization of this multitasking phenomenon by Rickettsiales as a strategy to maximize the use of their reduced protein repertoire is an emerging theme. Here, we provide an overview of the role of various moonlighting proteins in the pathogenicity of these species. Despite the challenges that lie ahead to determine the multiple potential faces of every single protein in Rickettsiales, the available examples anticipate this multifunctionality as an essential and intrinsic feature of these obligates and should be integrated into available moonlighting repositories.

PubMed: 35202227
DOI: 10.3390/tropicalmed7020032

Review

Authors: Emmanouil Angelakis, Yassina Bechah, Didier Raoult...

Epidemic typhus caused by Rickettsia prowazekii is one of the oldest pestilential diseases of humankind. The disease is transmitted to human beings by the body louse Pediculus humanus corporis and is still considered a major threat by public health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Epidemic typhus has accompanied disasters that impact humanity and has arguably determined the outcome of more wars than have soldiers and generals. The detection, identification, and characterization of microorganisms in ancient remains by paleomicrobiology has permitted the diagnosis of past epidemic typhus outbreaks through the detection of R. prowazekii. Various techniques, including microscopy and immunodetection, can be used in paleomicrobiology, but most of the data have been obtained by using PCR-based molecular techniques on dental pulp samples. Paleomicrobiology enabled the identification of the first outbreak of epidemic typhus in the 18th century in the context of a pan-European great war in the city of Douai, France, and supported the hypothesis that typhus was imported into Europe by Spanish soldiers returning from America. R. prowazekii was also detected in the remains of soldiers of Napoleon's Grand Army in Vilnius, Lithuania, which indicates that Napoleon's soldiers had epidemic typhus. The purpose of this article is to underscore the modern comprehension of clinical epidemic typhus, focus on the historical relationships of the disease, and examine the use of paleomicrobiology in the detection of past epidemic typhus outbreaks.

Topics: Animals; Bacteriological Techniques; Disease Outbreaks; Fossils; Global Health; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Paleopathology; Pediculus; Polymerase Chain Reaction; Rickettsia prowazekii; Typhus, Epidemic Louse-Borne

PubMed: 27726780
DOI: 10.1128/microbiolspec.PoH-0010-2015