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Didier Raoult - One of the best experts on this subject based on the ideXlab platform.
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The History of Epidemic Typhus
MICROBIOLOGY SPECTRUM, 2016Co-Authors: Emmanouil Angelakis, Yassina Bechah, Didier RaoultAbstract: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.
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AUTOCHTHONOUS Epidemic Typhus ASSOCIATED WITH BARTONELLA
2014Co-Authors: Homeless A Person, Philippe Brouqui, Sékéné Badiaga, Didier RaoultAbstract:Abstract. Trench fever, a louse-borne disease caused by Bartonella quintana, is reemerging in homeless persons. Epidemic Typhus is another life-threatening louse-borne disease caused by Rickettsia prowazekii and known to occur in conditions of war, famine, refugee camps, cold weather, poverty, or lapses in public health. We report the first case of seroconversion to R. prowazekii in a homeless person of Marseilles, France. This was associated with B. quintana bacteremia. Although no outbreaks of Typhus have been notified yet in the homeless population, this disease is likely to reemerge in such situation
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61 – Epidemic Louse-borne Typhus
2013Co-Authors: Aurélie Renvoisé, Didier RaoultAbstract:Abstract Epidemic Typhus is one of the oldest-known vector-borne human diseases. It is caused by Rickettsia prowazekii and is transmitted to humans, its main reservoir, by Pediculus humanus, the human body louse. However, flying squirrels and ticks may also play a role in the disease epidemiology. Epidemic Typhus has been responsible for large outbreaks in history, the latest being in Burundi in 1997. Associated with war and other catastrophic conditions that favor poor sanitary conditions with louse infestation, it is mostly described as a disease of cold areas where poverty, crowding, imprisonment, and civil unrest do not enable populations to change clothing. With a mortality that may reach 30% when untreated, Epidemic Typhus is the most severe rickettsiosis. Paradoxically, it may efficiently be treated with a single dose of oral doxycycline. The clinical diagnosis of Epidemic Typhus may not be easy, as symptoms are not pathognomonic, but serology using immunofluorescence may help confirm the diagnosis.
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61 Epidemic louse borne Typhus
Hunter's Tropical Medicine and Emerging Infectious Disease (Ninth Edition), 2013Co-Authors: Aurélie Renvoisé, Didier RaoultAbstract:Abstract Epidemic Typhus is one of the oldest-known vector-borne human diseases. It is caused by Rickettsia prowazekii and is transmitted to humans, its main reservoir, by Pediculus humanus, the human body louse. However, flying squirrels and ticks may also play a role in the disease epidemiology. Epidemic Typhus has been responsible for large outbreaks in history, the latest being in Burundi in 1997. Associated with war and other catastrophic conditions that favor poor sanitary conditions with louse infestation, it is mostly described as a disease of cold areas where poverty, crowding, imprisonment, and civil unrest do not enable populations to change clothing. With a mortality that may reach 30% when untreated, Epidemic Typhus is the most severe rickettsiosis. Paradoxically, it may efficiently be treated with a single dose of oral doxycycline. The clinical diagnosis of Epidemic Typhus may not be easy, as symptoms are not pathognomonic, but serology using immunofluorescence may help confirm the diagnosis.
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Brill-Zinsser disease in Moroccan man, France, 2011.
Emerging Infectious Diseases, 2012Co-Authors: Jean-françois Faucher, Catherine Chirouze, L. Hustache-mathieu, Cristina Socolovschi, Didier Raoult, Camille Aubry, Bruno HoenAbstract:To the Editor: Epidemic Typhus is caused by Rickettsia prowazekii and transmitted by human body lice. For centuries, it has been associated with overcrowding, cold weather, and poor hygiene. Brill-Zinsser disease is a recurrent form of Epidemic Typhus that is unrelated to louse infestation and develops sporadically years after the primary illness. Clinical features are similar to, but milder than, those of Epidemic Typhus (1). We report a case of Brill-Zinsser disease in a patient who was born in Morocco and had no history of Epidemic Typhus. A 69-year-old man living in France sought care from his general practitioner on March 7, 2011, after 2 days of high-grade fever (40°C) associated with headache, myalgia, fatigue, and mild cough. Amoxicillin was prescribed for a putative diagnosis of acute respiratory infection. He was admitted to hospital on March 9 for persistent fever. Physical examination results were unremarkable. Blood test results were as follows: C-reactive protein 111 mg/L (reference 0–8 mg/L); procalcitonin 0.49 ng/mL (reference 0.1–0.4 ng/mL), lymphocyte count 0.7 × 103 cells/μL (reference 1–4 × 103 cells/μL), platelet count 92 × 103 cells/μL (reference 150–450 × 103 cells/μL), and lactate dehydrogenase 376 U/L (reference 94–246 U/L). Chest radiograph results were normal. Results of 5 blood cultures and a urine culture were negative. Stupor developed on March 11. Cerebrospinal fluid test results were normal. Because the patient lived near a goat farm, Q fever and tularemia were considered plausible hypotheses, and oral doxycycline was introduced on March 13. The patient became afebrile on March 15, and he was discharged from the hospital and remained well. On the basis of serologic results, the following diagnoses could be ruled out: viral infections (HIV, cytomegalovirus, Epstein-Barr virus); tularemia; Q fever; leptospirosis; salmonellosis; and Legionella, Mycoplasma, and Chlamydia spp. infections. Acute-phase and convalescent-phase serum samples were positive for Typhus-group rickettsiae by the microimmunofluorescence assay at the World Health Organization Collaborative Center for Rickettsioses and Other Arthropod-Borne Bacterial Diseases (Marseille, France). A microimmunofluorescence assay showed titers of 100 for IgM and 6,400 for IgG. Western blot analyses and cross-adsorption studies strongly suggested R. prowazekii as the cause of the man’s illness. Quantitative PCR result on DNA extracted from the acute-phase serum was negative (2). The patient had been raised in Morocco. At 19 years of age, he emigrated to France, where he lived in a urban area. He subsequently traveled every 3 years to Morocco for 1-month summer holidays, always in urban areas. He had most recently traveled to Morocco in 2008. He denied any history of hospitalization for a severe febrile illness and any exposure to louse bites. In the weeks before disease onset, he had not taken any new drug. He had no immunoglobulin deficiency. On the basis of serologic analysis with Western blot, we confirmed R. prowazekii infection in a patient with no recent travel and no contact with lice or flying squirrels. R. prowazekii infection may occur rarely in France; it was found in Marseille in 2002 in an asymptomatic homeless person (3). In contrast, the patient in our report was living in a hygienic environment, and an autochthonous infection is therefore highly unlikely. Epidemic Typhus was endemic to North Africa until the 1970s (4). Subsequently, this region was thought to be free from Epidemic Typhus, but 2 cases have been reported since 1999 in Algeria, where 1 case of Brill-Zinsser disease was observed in a man who had had Epidemic Typhus in 1960 during the Algerian civil war (5–7). Few published data exist about the seroprevalence of R. prowazekii infections in North Africa (4). In Tunisia, no Epidemic Typhus was found in 2005 among 47 febrile patients (8). However, a seroepidemiologic survey performed in blood donors and hospitalized patients in the Aures, Algeria, found a prevalence of 2% (4). This finding suggests that R. prowazekii infection might have occurred in this population more often than suspected. No recent published data are available from Morocco. Since 1970, reports of only 8 cases of Brill-Zinsser disease have been published (9,10). In all cases, known risk factors were present (overcrowding, poor hygiene, or contact with flying squirrels). Brill and Zinsser described that stress or waning immunity could reactivate R. prowazekii infection (2). Corticosteroids can trigger recurrence of R. prowazekii in mice (2), but no such observations were made in humans. In the case presented here, we found no stress factor, no immunosuppression, and no medical history of Epidemic Typhus. Brill-Zinsser disease can develop >40 years after acute infection. The mechanism of R. prowazekii latency has not been established. A recently explored reservoir for silent forms of R. prowazekii infection is adipose tissue because it contains endothelial cells, which are the target cells for R. prowazekii infection, and because of its wide distribution throughout the body (2). Brill-Zinsser disease should be considered as a possible diagnosis for acute fever in any patient who has lived in an area where Epidemic Typhus is endemic.
David W. Stahle - One of the best experts on this subject based on the ideXlab platform.
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drought and Epidemic Typhus central mexico 1655 1918
Emerging Infectious Diseases, 2014Co-Authors: Jordan N. Burns, Rodolfo Acunasoto, David W. StahleAbstract:Epidemic Typhus is a serious infectious disease caused by the obligate, intracellular, gram-negative bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease is recognized for its high mortality rate throughout human history, particularly before modern sanitary practices and the availability of antimicrobial drugs (1). Typhus spreads where conditions are crowded and unsanitary. Historical Epidemics often followed war, climate extremes, famine, and social upheaval. Zinsser (2) noted that throughout history, Epidemic Typhus might have claimed more human lives during war than combat. Epidemic Typhus could reemerge as a serious infectious disease in areas of the world where social strife and underdeveloped public health programs persist (3). Typhus was first recorded in Mexico in 1655, and the most recent major Epidemic began in 1915 during the Mexican revolution. Mexico’s rich historical record of Epidemic disease is documented in archives of demographic data that include census records, health records, death certificates, and accounts of physicians. Mexico City and the high, densely populated valleys of central Mexico were particularly susceptible to smallpox, cholera, and Typhus Epidemics because of crowding and poor sanitation (4). Numerous Epidemics, some identified as Typhus, occurred during the colonial and early modern eras. We have compiled a record of 22 Typhus Epidemics in Mexico during 1655–1918. We compared the timing of these Typhus Epidemics with tree-ring reconstructions of growing-season moisture conditions to assess the relationship between climate and Typhus during this period.
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Drought and Epidemic Typhus, Central Mexico, 1655–1918
Emerging infectious diseases, 2014Co-Authors: Jordan N. Burns, Rodolfo Acuna-soto, David W. StahleAbstract:Epidemic Typhus is a serious infectious disease caused by the obligate, intracellular, gram-negative bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease is recognized for its high mortality rate throughout human history, particularly before modern sanitary practices and the availability of antimicrobial drugs (1). Typhus spreads where conditions are crowded and unsanitary. Historical Epidemics often followed war, climate extremes, famine, and social upheaval. Zinsser (2) noted that throughout history, Epidemic Typhus might have claimed more human lives during war than combat. Epidemic Typhus could reemerge as a serious infectious disease in areas of the world where social strife and underdeveloped public health programs persist (3). Typhus was first recorded in Mexico in 1655, and the most recent major Epidemic began in 1915 during the Mexican revolution. Mexico’s rich historical record of Epidemic disease is documented in archives of demographic data that include census records, health records, death certificates, and accounts of physicians. Mexico City and the high, densely populated valleys of central Mexico were particularly susceptible to smallpox, cholera, and Typhus Epidemics because of crowding and poor sanitation (4). Numerous Epidemics, some identified as Typhus, occurred during the colonial and early modern eras. We have compiled a record of 22 Typhus Epidemics in Mexico during 1655–1918. We compared the timing of these Typhus Epidemics with tree-ring reconstructions of growing-season moisture conditions to assess the relationship between climate and Typhus during this period.
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Drought and Epidemic Typhus, Central Mexico, 1655–1918
Centers for Disease Control and Prevention, 2014Co-Authors: Jordan N. Burns, Rodolfo Acuna-soto, David W. StahleAbstract:Epidemic Typhus is an infectious disease caused by the bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease occurs where conditions are crowded and unsanitary. This disease accompanied war, famine, and poverty for centuries. Historical and proxy climate data indicate that drought was a major factor in the development of Typhus Epidemics in Mexico during 1655–1918. Evidence was found for 22 large Typhus Epidemics in central Mexico, and tree-ring chronologies were used to reconstruct moisture levels over central Mexico for the past 500 years. Below-average tree growth, reconstructed drought, and low crop yields occurred during 19 of these 22 Typhus Epidemics. Historical documents describe how drought created large numbers of environmental refugees that fled the famine-stricken countryside for food relief in towns. These refugees often ended up in improvised shelters in which crowding encouraged conditions necessary for spread of Typhus
Yassina Bechah - One of the best experts on this subject based on the ideXlab platform.
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The History of Epidemic Typhus
MICROBIOLOGY SPECTRUM, 2016Co-Authors: Emmanouil Angelakis, Yassina Bechah, Didier RaoultAbstract: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.
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rickettsial diseases from rickettsia arthropod relationships to pathophysiology and animal models
Future Microbiology, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Rickettsiae cause spotted fevers and Typhus-related diseases in humans. Some of these diseases occur worldwide and are life-threatening, for example, Epidemic Typhus is still a major health problem despite the apparent efficiency of antibiotic treatment. In addition, Rickettsia prowazekii, the agent of Epidemic Typhus, and R. rickettsii, the agent of Rocky Mountain spotted fever, are microorganisms that could potentially be used as bioweapons to induce panic in the population. Rickettsiae are obligate intracellular bacteria in both vertebrate and invertebrate hosts, but rickettsial species differ in terms of association with arthropods, behavior of the vector to infection, pathophysiology and outcome of the disease. Understanding the pathogenic steps of rickettsioses is essential to develop protective strategies against these bacteriological threats. Unfortunately, the mechanisms involved in the pathogenesis of many rickettsioses are poorly characterized, and protective immunity is incompletely understood...
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Epidemic Typhus.
The Lancet. Infectious diseases, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Epidemic Typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of Epidemic Typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new Epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of Epidemic Typhus may be useful for protection against this bacterial threat.
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Infection of Endothelial Cells with Virulent Rickettsia prowazekii Increases the Transmigration of Leukocytes
The Journal of infectious diseases, 2008Co-Authors: Yassina Bechah, Didier Raoult, Christian Capo, Jean-louis MegeAbstract:Rickettsia prowazekii, the etiologic agent of Epidemic Typhus, infects vascular endothelium, leading to vasculitis and tissue infiltration of leukocytes. Murine and human endothelial cells (ECs) were infected with R. prowazekii, including the virulent Breinl strain and the attenuated Madrid E strain. The transendothelial migration (TM) of murine and human peripheral blood mononuclear cells (PBMCs) across ECs infected with Breinl organisms was significantly increased compared with that for uninfected ECs or for ECs infected with attenuated organisms, demonstrating that increased TM was related to R. prowazekii virulence. Increased TM was associated with a specific inflammatory pattern. Indeed, only Breinl organisms induced the expression of transcripts for inflammatory cytokines and chemokines by ECs. Murine PBMCs that had transmigrated across ECs infected with Breinl organisms overexpressed inflammatory cytokines and chemokines as well as tissue factor, whereas interleukin-10 expression was down-regulated. The impact of R. prowazekii infection on the TM of PBMCs may play a prominent role in the development of lesions in Epidemic Typhus.
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Rickettsial diseases: from Rickettsia–arthropod relationships to pathophysiology and animal models
Future microbiology, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Rickettsiae cause spotted fevers and Typhus-related diseases in humans. Some of these diseases occur worldwide and are life-threatening, for example, Epidemic Typhus is still a major health problem despite the apparent efficiency of antibiotic treatment. In addition, Rickettsia prowazekii, the agent of Epidemic Typhus, and R. rickettsii, the agent of Rocky Mountain spotted fever, are microorganisms that could potentially be used as bioweapons to induce panic in the population. Rickettsiae are obligate intracellular bacteria in both vertebrate and invertebrate hosts, but rickettsial species differ in terms of association with arthropods, behavior of the vector to infection, pathophysiology and outcome of the disease. Understanding the pathogenic steps of rickettsioses is essential to develop protective strategies against these bacteriological threats. Unfortunately, the mechanisms involved in the pathogenesis of many rickettsioses are poorly characterized, and protective immunity is incompletely understood, in part because accurate animal models that mimic human diseases are lacking. In the past, murine models have been of limited value because infection of mice was without effect or resulted in erratic mortality. Recent studies have reported that rickettsial infection can be established in mice, depending on the genetic background of mice, the type of rickettsial species and the route of inoculation. These models may be useful for analyzing the pathogenesis of rickettsioses, especially Epidemic Typhus, evaluating new therapeutic molecules and vaccine candidates, and preventing future outbreaks.
Jordan N. Burns - One of the best experts on this subject based on the ideXlab platform.
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drought and Epidemic Typhus central mexico 1655 1918
Emerging Infectious Diseases, 2014Co-Authors: Jordan N. Burns, Rodolfo Acunasoto, David W. StahleAbstract:Epidemic Typhus is a serious infectious disease caused by the obligate, intracellular, gram-negative bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease is recognized for its high mortality rate throughout human history, particularly before modern sanitary practices and the availability of antimicrobial drugs (1). Typhus spreads where conditions are crowded and unsanitary. Historical Epidemics often followed war, climate extremes, famine, and social upheaval. Zinsser (2) noted that throughout history, Epidemic Typhus might have claimed more human lives during war than combat. Epidemic Typhus could reemerge as a serious infectious disease in areas of the world where social strife and underdeveloped public health programs persist (3). Typhus was first recorded in Mexico in 1655, and the most recent major Epidemic began in 1915 during the Mexican revolution. Mexico’s rich historical record of Epidemic disease is documented in archives of demographic data that include census records, health records, death certificates, and accounts of physicians. Mexico City and the high, densely populated valleys of central Mexico were particularly susceptible to smallpox, cholera, and Typhus Epidemics because of crowding and poor sanitation (4). Numerous Epidemics, some identified as Typhus, occurred during the colonial and early modern eras. We have compiled a record of 22 Typhus Epidemics in Mexico during 1655–1918. We compared the timing of these Typhus Epidemics with tree-ring reconstructions of growing-season moisture conditions to assess the relationship between climate and Typhus during this period.
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Drought and Epidemic Typhus, Central Mexico, 1655–1918
Emerging infectious diseases, 2014Co-Authors: Jordan N. Burns, Rodolfo Acuna-soto, David W. StahleAbstract:Epidemic Typhus is a serious infectious disease caused by the obligate, intracellular, gram-negative bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease is recognized for its high mortality rate throughout human history, particularly before modern sanitary practices and the availability of antimicrobial drugs (1). Typhus spreads where conditions are crowded and unsanitary. Historical Epidemics often followed war, climate extremes, famine, and social upheaval. Zinsser (2) noted that throughout history, Epidemic Typhus might have claimed more human lives during war than combat. Epidemic Typhus could reemerge as a serious infectious disease in areas of the world where social strife and underdeveloped public health programs persist (3). Typhus was first recorded in Mexico in 1655, and the most recent major Epidemic began in 1915 during the Mexican revolution. Mexico’s rich historical record of Epidemic disease is documented in archives of demographic data that include census records, health records, death certificates, and accounts of physicians. Mexico City and the high, densely populated valleys of central Mexico were particularly susceptible to smallpox, cholera, and Typhus Epidemics because of crowding and poor sanitation (4). Numerous Epidemics, some identified as Typhus, occurred during the colonial and early modern eras. We have compiled a record of 22 Typhus Epidemics in Mexico during 1655–1918. We compared the timing of these Typhus Epidemics with tree-ring reconstructions of growing-season moisture conditions to assess the relationship between climate and Typhus during this period.
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Drought and Epidemic Typhus, Central Mexico, 1655–1918
Centers for Disease Control and Prevention, 2014Co-Authors: Jordan N. Burns, Rodolfo Acuna-soto, David W. StahleAbstract:Epidemic Typhus is an infectious disease caused by the bacterium Rickettsia prowazekii and transmitted by body lice (Pediculus humanus corporis). This disease occurs where conditions are crowded and unsanitary. This disease accompanied war, famine, and poverty for centuries. Historical and proxy climate data indicate that drought was a major factor in the development of Typhus Epidemics in Mexico during 1655–1918. Evidence was found for 22 large Typhus Epidemics in central Mexico, and tree-ring chronologies were used to reconstruct moisture levels over central Mexico for the past 500 years. Below-average tree growth, reconstructed drought, and low crop yields occurred during 19 of these 22 Typhus Epidemics. Historical documents describe how drought created large numbers of environmental refugees that fled the famine-stricken countryside for food relief in towns. These refugees often ended up in improvised shelters in which crowding encouraged conditions necessary for spread of Typhus
Jean-louis Mege - One of the best experts on this subject based on the ideXlab platform.
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rickettsial diseases from rickettsia arthropod relationships to pathophysiology and animal models
Future Microbiology, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Rickettsiae cause spotted fevers and Typhus-related diseases in humans. Some of these diseases occur worldwide and are life-threatening, for example, Epidemic Typhus is still a major health problem despite the apparent efficiency of antibiotic treatment. In addition, Rickettsia prowazekii, the agent of Epidemic Typhus, and R. rickettsii, the agent of Rocky Mountain spotted fever, are microorganisms that could potentially be used as bioweapons to induce panic in the population. Rickettsiae are obligate intracellular bacteria in both vertebrate and invertebrate hosts, but rickettsial species differ in terms of association with arthropods, behavior of the vector to infection, pathophysiology and outcome of the disease. Understanding the pathogenic steps of rickettsioses is essential to develop protective strategies against these bacteriological threats. Unfortunately, the mechanisms involved in the pathogenesis of many rickettsioses are poorly characterized, and protective immunity is incompletely understood...
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Epidemic Typhus.
The Lancet. Infectious diseases, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Epidemic Typhus is transmitted to human beings by the body louse Pediculus humanus corporis. The disease is still considered a major threat by public-health authorities, despite the efficacy of antibiotics, because poor sanitary conditions are conducive to louse proliferation. Until recently, Rickettsia prowazekii, the causal agent, was thought to be confined to human beings and their body lice. Since 1975, R prowazekii infection in human beings has been related to contact with the flying squirrel Glaucomys volans in the USA. Moreover, Brill-Zinsser disease, a relapsed form of Epidemic Typhus that appears as sporadic cases many years after the initial infection, is unrelated to louse infestation. Stress or a waning immune system are likely to reactivate this earlier persistent infection, which could be the source of new Epidemics when conditions facilitate louse infestation. Finally, R prowazekii is a potential category B bioterrorism agent, because it is stable in dried louse faeces and can be transmitted through aerosols. An increased understanding of the pathogenesis of Epidemic Typhus may be useful for protection against this bacterial threat.
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Infection of Endothelial Cells with Virulent Rickettsia prowazekii Increases the Transmigration of Leukocytes
The Journal of infectious diseases, 2008Co-Authors: Yassina Bechah, Didier Raoult, Christian Capo, Jean-louis MegeAbstract:Rickettsia prowazekii, the etiologic agent of Epidemic Typhus, infects vascular endothelium, leading to vasculitis and tissue infiltration of leukocytes. Murine and human endothelial cells (ECs) were infected with R. prowazekii, including the virulent Breinl strain and the attenuated Madrid E strain. The transendothelial migration (TM) of murine and human peripheral blood mononuclear cells (PBMCs) across ECs infected with Breinl organisms was significantly increased compared with that for uninfected ECs or for ECs infected with attenuated organisms, demonstrating that increased TM was related to R. prowazekii virulence. Increased TM was associated with a specific inflammatory pattern. Indeed, only Breinl organisms induced the expression of transcripts for inflammatory cytokines and chemokines by ECs. Murine PBMCs that had transmigrated across ECs infected with Breinl organisms overexpressed inflammatory cytokines and chemokines as well as tissue factor, whereas interleukin-10 expression was down-regulated. The impact of R. prowazekii infection on the TM of PBMCs may play a prominent role in the development of lesions in Epidemic Typhus.
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Rickettsial diseases: from Rickettsia–arthropod relationships to pathophysiology and animal models
Future microbiology, 2008Co-Authors: Yassina Bechah, Christian Capo, Jean-louis Mege, Didier RaoultAbstract:Rickettsiae cause spotted fevers and Typhus-related diseases in humans. Some of these diseases occur worldwide and are life-threatening, for example, Epidemic Typhus is still a major health problem despite the apparent efficiency of antibiotic treatment. In addition, Rickettsia prowazekii, the agent of Epidemic Typhus, and R. rickettsii, the agent of Rocky Mountain spotted fever, are microorganisms that could potentially be used as bioweapons to induce panic in the population. Rickettsiae are obligate intracellular bacteria in both vertebrate and invertebrate hosts, but rickettsial species differ in terms of association with arthropods, behavior of the vector to infection, pathophysiology and outcome of the disease. Understanding the pathogenic steps of rickettsioses is essential to develop protective strategies against these bacteriological threats. Unfortunately, the mechanisms involved in the pathogenesis of many rickettsioses are poorly characterized, and protective immunity is incompletely understood, in part because accurate animal models that mimic human diseases are lacking. In the past, murine models have been of limited value because infection of mice was without effect or resulted in erratic mortality. Recent studies have reported that rickettsial infection can be established in mice, depending on the genetic background of mice, the type of rickettsial species and the route of inoculation. These models may be useful for analyzing the pathogenesis of rickettsioses, especially Epidemic Typhus, evaluating new therapeutic molecules and vaccine candidates, and preventing future outbreaks.
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A murine model of infection with Rickettsia prowazekii: implications for pathogenesis of Epidemic Typhus
Microbes and infection, 2007Co-Authors: Yassina Bechah, Didier Raoult, Christian Capo, Georges E. Grau, Jean-louis MegeAbstract:Epidemic Typhus remains a major disease threat, furthermore, its etiologic agent, Rickettsia prowazekii, is classified as a bioterrorism agent. We describe here a murine model of Epidemic Typhus that reproduced some features of the human disease. When BALB/c mice were inoculated intravenously with R. prowazekii (Breinl strain), they survived but did not clear R. prowazekii infection. Immunohistological analysis of tissues and quantitative PCR showed that R. prowazekii was present in blood, liver, lungs and brain 1 day after infection and persisted for at least 9 days. Importantly, infected mice developed interstitial pneumonia, with consolidation of the alveoli, hemorrhages in lungs, multifocal granulomas in liver, and hemorrhages in brain, as seen in humans. Circulating antibodies directed against R. prowazekii were detected at day 4 post-infection and steadily increased for up to 21 days, demonstrating that R. prowazekii lesions were independent of humoral immune response. R. prowazekii-induced lesions were associated with inflammatory response, as demonstrated by elevated levels of inflammatory cytokines including interferon-gamma, tumor necrosis factor and the CC chemokine RANTES in the lesions. We concluded that the BALB/c mouse strain provides a useful model for studying the pathogenic mechanisms of Epidemic Typhus and its control by the immune system.