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Paul N. Newton - One of the best experts on this subject based on the ideXlab platform.
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estimating the burden of scrub Typhus a systematic review
PLOS Neglected Tropical Diseases, 2017Co-Authors: Ana Bonell, Paul N. Newton, Yoel Lubell, John A Crump, Daniel H ParisAbstract:Background Scrub Typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub Typhus remains poorly known. Methods We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub Typhus since the year 2000. Findings In prospective fever studies from Asia, scrub Typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub Typhus. Limited evidence suggests high mortality in complicated scrub Typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes. Interpretation Scrub Typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub Typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub Typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.
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Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos.
PLoS neglected tropical diseases, 2015Co-Authors: Daniel H Paris, Paul N. Newton, Femke Stephan, Ingrid Bulder, Diana Wouters, Tom Van Der Poll, Nicholas P. J. Day, Sacha ZeerlederAbstract:Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil activation, as evidenced by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub Typhus and murine Typhus. In acute scrub Typhus elevated nucleosome levels correlated with lower GCS scores, raised respiratory rate, jaundice and impaired liver function, whereas neutrophil activation correlated with fibrinolysis and high IL-8 plasma levels, a recently identified predictor of severe disease and mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and 4-fold increased risk of developing severe scrub Typhus, beyond cut off values of 1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine Typhus, nucleosome levels associated with pro-inflammatory cytokines and the duration of illness, while ELA complexes correlated strongly with inflammation markers, jaundice and increased respiratory rates. This study found strong correlations between circulating nucleosomes and neutrophil activation in patients with scrub Typhus, but not murine Typhus, providing indirect evidence that nucleosomes could originate from neutrophil extracellular trap (NET) degradation. High circulating plasma nucleosomes and ELA complexes represent independent risk factors for developing severe complications in scrub Typhus. As nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could contribute to vascular damage, the pro-coagulant state and exacerbation of disease in scrub Typhus, thus indicating a detrimental role of neutrophil activation. The data suggest that increased neutrophil activation relates to disease progression and severe complications, and increased plasma levels of nucleosomes and ELA complexes represent independent risk factors for developing severe scrub Typhus.
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concurrent infection with murine Typhus and scrub Typhus in southern laos the mixed and the unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Josee Castonguayvanier, Sommay Keomany, Phoutthalavanh Souvannasing, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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Concurrent Infection with Murine Typhus and Scrub Typhus in Southern Laos—the Mixed and the Unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Sommay Keomany, Phoutthalavanh Souvannasing, Josée Castonguay-vanier, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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Coagulation and inflammation in scrub Typhus and murine Typhus—a prospective comparative study from Laos
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2011Co-Authors: Daniel H Paris, Stuart D Blacksell, Paul N. Newton, Vilada Chansamouth, Pruksa Nawtaisong, Ester C. Löwenberg, Rattanaphone Phetsouvanh, Sue Jean Lee, Arjen M. Dondorp, T. Van Der PollAbstract:Scrub Typhus (caused by Orientia tsutsugamushi) and murine Typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub Typhus, 55 murine Typhus, and 11 Typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in Typhus patients; however, the activation patterns differed significantly between scrub and murine Typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub Typhus than in those with murine Typhus. In patients with murine Typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both Typhus patient groups. This is the first study demonstrating that, in scrub Typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine Typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.
Daniel H Paris - One of the best experts on this subject based on the ideXlab platform.
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Diagnosis of Murine Typhus by Serology in Peninsular Malaysia: A Case Report Where Rickettsial Illnesses, Leptospirosis and Dengue Co-Circulate
MDPI AG, 2019Co-Authors: Yazli Yuhana, Daniel H Paris, Stuart D Blacksell, Ampai Tanganuchitcharnchai, Pimpan Sujariyakul, Piengchan Sonthayanon, Kesinee Chotivanich, Sasithon Pukrittayakamee, Borimas HanboonkunupakarnAbstract:Murine Typhus is a rarely diagnosed cause of acute febrile illness in Malaysia, and its true disease burden is unknown. We report a case of an acute murine Typhus infection in a patient living in a small city in Peninsular Malaysia, presenting with fever, rash, and headache. Unresponsive to the initial empirical treatment for leptospirosis, he showed a rapid response to doxycycline when murine Typhus was diagnosed later. This case highlights the importance of considering murine Typhus as a diagnostic in cases of acute febrile illness in urban and sub-urban areas, such as that of in Peninsular Malaysia
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estimating the burden of scrub Typhus a systematic review
PLOS Neglected Tropical Diseases, 2017Co-Authors: Ana Bonell, Paul N. Newton, Yoel Lubell, John A Crump, Daniel H ParisAbstract:Background Scrub Typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub Typhus remains poorly known. Methods We systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub Typhus since the year 2000. Findings In prospective fever studies from Asia, scrub Typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%–27.9% (median 22.2% IQR 18.6–25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub Typhus. Limited evidence suggests high mortality in complicated scrub Typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes. Interpretation Scrub Typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8–10 years from countries with an established surveillance system. A wider distribution of scrub Typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub Typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.
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Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos.
PLoS neglected tropical diseases, 2015Co-Authors: Daniel H Paris, Paul N. Newton, Femke Stephan, Ingrid Bulder, Diana Wouters, Tom Van Der Poll, Nicholas P. J. Day, Sacha ZeerlederAbstract:Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil activation, as evidenced by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub Typhus and murine Typhus. In acute scrub Typhus elevated nucleosome levels correlated with lower GCS scores, raised respiratory rate, jaundice and impaired liver function, whereas neutrophil activation correlated with fibrinolysis and high IL-8 plasma levels, a recently identified predictor of severe disease and mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and 4-fold increased risk of developing severe scrub Typhus, beyond cut off values of 1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine Typhus, nucleosome levels associated with pro-inflammatory cytokines and the duration of illness, while ELA complexes correlated strongly with inflammation markers, jaundice and increased respiratory rates. This study found strong correlations between circulating nucleosomes and neutrophil activation in patients with scrub Typhus, but not murine Typhus, providing indirect evidence that nucleosomes could originate from neutrophil extracellular trap (NET) degradation. High circulating plasma nucleosomes and ELA complexes represent independent risk factors for developing severe complications in scrub Typhus. As nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could contribute to vascular damage, the pro-coagulant state and exacerbation of disease in scrub Typhus, thus indicating a detrimental role of neutrophil activation. The data suggest that increased neutrophil activation relates to disease progression and severe complications, and increased plasma levels of nucleosomes and ELA complexes represent independent risk factors for developing severe scrub Typhus.
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concurrent infection with murine Typhus and scrub Typhus in southern laos the mixed and the unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Josee Castonguayvanier, Sommay Keomany, Phoutthalavanh Souvannasing, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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Concurrent Infection with Murine Typhus and Scrub Typhus in Southern Laos—the Mixed and the Unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Sommay Keomany, Phoutthalavanh Souvannasing, Josée Castonguay-vanier, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
Stuart D Blacksell - One of the best experts on this subject based on the ideXlab platform.
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Diagnosis of Murine Typhus by Serology in Peninsular Malaysia: A Case Report Where Rickettsial Illnesses, Leptospirosis and Dengue Co-Circulate
MDPI AG, 2019Co-Authors: Yazli Yuhana, Daniel H Paris, Stuart D Blacksell, Ampai Tanganuchitcharnchai, Pimpan Sujariyakul, Piengchan Sonthayanon, Kesinee Chotivanich, Sasithon Pukrittayakamee, Borimas HanboonkunupakarnAbstract:Murine Typhus is a rarely diagnosed cause of acute febrile illness in Malaysia, and its true disease burden is unknown. We report a case of an acute murine Typhus infection in a patient living in a small city in Peninsular Malaysia, presenting with fever, rash, and headache. Unresponsive to the initial empirical treatment for leptospirosis, he showed a rapid response to doxycycline when murine Typhus was diagnosed later. This case highlights the importance of considering murine Typhus as a diagnostic in cases of acute febrile illness in urban and sub-urban areas, such as that of in Peninsular Malaysia
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concurrent infection with murine Typhus and scrub Typhus in southern laos the mixed and the unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Josee Castonguayvanier, Sommay Keomany, Phoutthalavanh Souvannasing, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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Concurrent Infection with Murine Typhus and Scrub Typhus in Southern Laos—the Mixed and the Unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Sommay Keomany, Phoutthalavanh Souvannasing, Josée Castonguay-vanier, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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coagulation and inflammation in scrub Typhus and murine Typhus a prospective comparative study from laos
Clinical Microbiology and Infection, 2012Co-Authors: Daniel H Paris, Stuart D Blacksell, Vilada Chansamouth, Pruksa Nawtaisong, Ester C. Löwenberg, Rattanaphone Phetsouvanh, Sue Jean Lee, Arjen M. DondorpAbstract:Scrub Typhus (caused by Orientia tsutsugamushi) and murine Typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub Typhus, 55 murine Typhus, and 11 Typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in Typhus patients; however, the activation patterns differed significantly between scrub and murine Typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub Typhus than in those with murine Typhus. In patients with murine Typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both Typhus patient groups. This is the first study demonstrating that, in scrub Typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine Typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.
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Coagulation and inflammation in scrub Typhus and murine Typhus—a prospective comparative study from Laos
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2011Co-Authors: Daniel H Paris, Stuart D Blacksell, Paul N. Newton, Vilada Chansamouth, Pruksa Nawtaisong, Ester C. Löwenberg, Rattanaphone Phetsouvanh, Sue Jean Lee, Arjen M. Dondorp, T. Van Der PollAbstract:Scrub Typhus (caused by Orientia tsutsugamushi) and murine Typhus (caused by Rickettsia typhi) cause up to 28% of febrile episodes in Thailand and Laos. The current understanding of coagulation and inflammation in the pathogenesis of these clinically very similar vasculotropic diseases is limited. This study compared human in vivo changes in 15 coagulation, inflammation and endothelial activation markers in prospectively collected admission and follow-up samples of 121 patients (55 scrub Typhus, 55 murine Typhus, and 11 Typhus-like illness) and 51 healthy controls from Laos. As compared with controls, all but one of the markers assessed were significantly affected in Typhus patients; however, the activation patterns differed significantly between scrub and murine Typhus patients. The levels of markers of coagulation activation and all inflammatory cytokines, except for interleukin-12, were significantly higher in patients with scrub Typhus than in those with murine Typhus. In patients with murine Typhus, however, the levels of endothelium-derived markers were significantly higher. Anticoagulant factors were inhibited in both Typhus patient groups. This is the first study demonstrating that, in scrub Typhus, in vivo coagulation activation is prominent and is related to a strong proinflammatory response, whereas in murine Typhus, changes in coagulant and fibrinolytic pathways are suggestive of endothelial cell perturbation. These data suggest that, although late-stage endothelial infection is common in both diseases, the in vivo pathogenic mechanisms of R. typhi and O. tsutsugamushi could differ in the early phase of infection and may contribute to disease differentiation.
Koukeo Phommasone - One of the best experts on this subject based on the ideXlab platform.
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concurrent infection with murine Typhus and scrub Typhus in southern laos the mixed and the unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Josee Castonguayvanier, Sommay Keomany, Phoutthalavanh Souvannasing, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
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Concurrent Infection with Murine Typhus and Scrub Typhus in Southern Laos—the Mixed and the Unmixed
PLOS Neglected Tropical Diseases, 2013Co-Authors: Koukeo Phommasone, Daniel H Paris, Tippawan Anantatat, Sommay Keomany, Phoutthalavanh Souvannasing, Josée Castonguay-vanier, Mayfong Mayxay, Stuart D Blacksell, Paul N. NewtonAbstract:Scrub Typhus, murine Typhus, and spotted fever group rickettsia all occur in the Lao PDR (Laos) [1], [2]. Scrub Typhus and murine Typhus account for ∼16% and 10%, respectively, of acute undifferentiated fever in blood culture–negative adults admitted to hospital in the capital city, Vientiane [1]. However, Typhus-like illnesses are significant diagnostic challenges; patients with leptospirosis, dengue, typhoid, and malaria are also common and can present with similar symptoms and signs. Although these pathogens are common and mixed (or concurrent) infections are expected, the laboratory diagnosis of mixed infection is a vexed subject. Reports of mixed infections often use only serological criteria. The problems of antibody persistence and interspecies cross-reaction raise uncertainty as to whether these results represent true mixed infections, sequential infections, or cross-reactions. We report a patient with concurrent scrub Typhus and murine Typhus, demonstrated by dual PCR positivity, and discuss evidence for identifying mixed infections.
Allen L. Richards - One of the best experts on this subject based on the ideXlab platform.
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Imported scrub Typhus: first case in South America and review of the literature
Tropical Diseases Travel Medicine and Vaccines, 2018Co-Authors: Thomas Weitzel, Mabel Aylwin, Constanza Martínez-valdebenito, Ju Jiang, Jose Manuel Munita, Luis Thompson, Katia Abarca, Allen L. RichardsAbstract:Background Scrub Typhus is a neglected vector-borne zoonosis causing life-threatening illnesses, endemic in the Asian-Pacific region and, as recently discovered, in southern Chile. Scrub Typhus is rarely reported in travelers, most probably due to the lack of clinical experience and diagnostic tests in non-endemic countries. We report the first case of imported scrub Typhus in South America. Case presentation A 62-year-old tourist from South Korea presented severely ill with fever, rash, and eschar in Santiago, Chile. Laboratory exams showed thrombocytopenia and elevated inflammation parameters, hepatic enzymes, and LDH. With the clinical suspicion of scrub Typhus, empirical treatment with doxycycline was initiated and the patient recovered rapidly and without complications. The diagnosis was confirmed by IgM serology and by real-time PCR, which demonstrated infection with Orientia tsutsugamushi (Kawasaki clade). Conclusions Only due to the emerging clinical experience with endemic South American scrub Typhus and the recent implementation of appropriate diagnostic techniques in Chile, were we able to firstly identify and adequately manage a severe case of imported scrub Typhus in South America. Physicians attending febrile travelers need to be aware of this rickettsiosis, since it requires prompt treatment with doxycycline to avoid complications.
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imported scrub Typhus first case in south america and review of the literature
Tropical Diseases Travel Medicine and Vaccines, 2018Co-Authors: Thomas Weitzel, Allen L. Richards, Mabel Aylwin, Ju Jiang, Jose Manuel Munita, Luis Thompson, Katia Abarca, Constanza MartinezvaldebenitoAbstract:Scrub Typhus is a neglected vector-borne zoonosis causing life-threatening illnesses, endemic in the Asian-Pacific region and, as recently discovered, in southern Chile. Scrub Typhus is rarely reported in travelers, most probably due to the lack of clinical experience and diagnostic tests in non-endemic countries. We report the first case of imported scrub Typhus in South America. A 62-year-old tourist from South Korea presented severely ill with fever, rash, and eschar in Santiago, Chile. Laboratory exams showed thrombocytopenia and elevated inflammation parameters, hepatic enzymes, and LDH. With the clinical suspicion of scrub Typhus, empirical treatment with doxycycline was initiated and the patient recovered rapidly and without complications. The diagnosis was confirmed by IgM serology and by real-time PCR, which demonstrated infection with Orientia tsutsugamushi (Kawasaki clade). Only due to the emerging clinical experience with endemic South American scrub Typhus and the recent implementation of appropriate diagnostic techniques in Chile, were we able to firstly identify and adequately manage a severe case of imported scrub Typhus in South America. Physicians attending febrile travelers need to be aware of this rickettsiosis, since it requires prompt treatment with doxycycline to avoid complications.
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Contrasting Spatial Distribution and Risk Factors for Past Infection with Scrub Typhus and Murine Typhus in Vientiane City, Lao PDR
PLoS neglected tropical diseases, 2010Co-Authors: Julie Vallée, Rattanaphone Phetsouvanh, Thaksinaporn Thaojaikong, Catrin E. Moore, Allen L. Richards, Marc Souris, Florence Fournet, Gérard Salem, Jean-paul J. Gonzalez, Paul N. NewtonAbstract:Background: The aetiological diagnostic of fevers in Laos remains difficult due to limited laboratory diagnostic facilities. However, it has recently become apparent that both scrub and murine Typhus are common causes of previous undiagnosed fever. Epidemiological data suggests that scrub Typhus would be more common in rural areas and murine Typhus in urban areas, but there is very little recent information on factors involved in scrub and murine Typhus transmission, especially where they are sympatric - as is the case in Vientiane, the capital of the Lao PDR. Methodology and Principal Findings: We therefore determined the frequency of IgG seropositivity against scrub Typhus (Orientia tsutsugamushi) and murine Typhus (Rickettsia typhi), as indices of prior exposure to these pathogens, in randomly selected adults in urban and peri-urban Vientiane City (n=2,002, $35 years). Anti-scrub and murine Typhus IgG were detected by ELISA assays using filter paper elutes. We validated the accuracy of ELISA of these elutes against ELISA using serum samples. The overall prevalence of scrub and murine Typhus IgG antibodies was 20.3% and 20.6%, respectively. Scrub Typhus seropositivity was significantly higher among adults living in the periphery (28.4%) than in the central zone (13.1%) of Vientiane. In contrast, seroprevalence of murine Typhus IgG antibodies was significantly higher in the central zone (30.8%) as compared to the periphery (14.4%). In multivariate analysis, adults with a longer residence in Vientiane were at significant greater risk of past infection with murine Typhus and at lower risk for scrub Typhus. Those with no education, living on low incomes, living on plots of land with poor sanitary conditions, living in large households, and farmers were at higher risk of scrub Typhus and those living in neighborhoods with high building density and close to markets were at greater risk for murine Typhus and at lower risk of scrub Typhus past infection. Conclusions: This study underscores the intense circulation of both scrub and murine Typhus in Vientiane city and underlines difference in spatial distribution and risk factors involved in the transmission of these diseases.
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Murine Typhus and Febrile Illness, Nepal
Emerging infectious diseases, 2008Co-Authors: Mark Zimmerman, Allen L. Richards, David R. Murdoch, Patrick J. Rozmajzl, Basnyat, Christopher W. Woods, Ram Hari Belbase, David A. Hammer, Trevor P. Anderson, L. Barth RellerAbstract:Murine Typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine Typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished Typhus patients from those with blood culture–positive enteric fever.
