RESUMO
Epidemic typhus, caused by Rickettsia prowazekii bacteria and transmitted through body lice (Pediculus humanus corporis), was a major public health threat in Eastern Europe as a consequence of World War II. In 2022, war and the resulting population displacement in Ukraine risks the return of this serious disease.
Assuntos
Infestações por Piolhos , Pediculus , Rickettsia prowazekii , Tifo Epidêmico Transmitido por Piolhos , Animais , Humanos , Pediculus/microbiologia , Tifo Epidêmico Transmitido por Piolhos/epidemiologia , Tifo Epidêmico Transmitido por Piolhos/história , Tifo Epidêmico Transmitido por Piolhos/microbiologia , Ucrânia/epidemiologiaRESUMO
Scrub typhus, a neglected infectious disease caused by the obligate intracellular bacterium Orientia tsutsugamushi, is a major cause of fever across the Asia Pacific region with more than a billion people at risk. Treatment with antibiotics such as doxycycline or chloramphenicol is effective for the majority of patients. In the 1990s, reports from northern Thailand raised a troubling observation; some scrub typhus patients responded poorly to doxycycline, which investigators attributed to doxycycline resistance. Despite the controversial nature of these reports, independent verification was neglected, with subsequent studies speculating on the role of doxycycline resistance in contributing to failure of treatment or prophylaxis. In this review, we have outlined the evidence for drug-resistant Orientia tsutsugamushi, assessed the evidence for doxycycline resistance, and highlight more recent findings unsupportive of doxycycline resistance. We conclude that doxycycline resistance is a misconception, with treatment outcome likely to be determined by other bacterial, host, and pharmacological factors.
Assuntos
Orientia tsutsugamushi , Tifo por Ácaros , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Humanos , Tifo por Ácaros/tratamento farmacológico , TailândiaRESUMO
Scrub typhus is a potentially fatal rickettsiosis caused by Orientia species intracellular bacteria of the genus Orientia. Although considered to be restricted to the Asia Pacific region, scrub typhus has recently been discovered in southern Chile. We analyzed Orientia gene sequences of 16S rRNA (rrs) and 47-kDa (htrA) from 18 scrub typhus patients from Chile. Sequences were ≥99.7% identical among the samples for both amplified genes. Their diversity was 3.1%-3.5% for rrs and 11.2%-11.8% for htrA compared with O. tsusugamushi and 3.0% for rrs and 14.8% for htrA compared with Candidatus Orientia chuto. Phylogenetic analyses of both genes grouped the specimens from Chile in a different clade from other Orientia species. Our results indicate that Orientia isolates from Chile constitute a novel species, which, until they are cultivated and fully characterized, we propose to designate as Candidatus Orientia chiloensis, after the Chiloé Archipelago where the pathogen was identified.
Assuntos
Orientia tsutsugamushi , Tifo por Ácaros , Ásia , Chile/epidemiologia , Humanos , Orientia , Orientia tsutsugamushi/genética , Filogenia , RNA Ribossômico 16S/genética , Tifo por Ácaros/epidemiologiaRESUMO
Endemic scrub typhus was recently detected on Chiloé Island in southern Chile. We report a series of cases, acquired over a wide geographical range in continental Chile during 2016-2018, demonstrating that this emerging rickettsial infection is also found on the mainland of South America.
Assuntos
Orientia tsutsugamushi , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/microbiologia , Adulto , Idoso , Animais , Chile/epidemiologia , Feminino , História do Século XXI , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Orientia tsutsugamushi/genética , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/história , Tifo por Ácaros/transmissão , Doenças Transmitidas por Vetores , Adulto Jovem , ZoonosesRESUMO
Rickettsioses are endemic to Vietnam; however, only a limited number of clinical studies have been performed on these vectorborne bacteria. We conducted a prospective hospital-based study at 2 national referral hospitals in Hanoi to describe the clinical characteristics of scrub typhus and murine typhus in northern Vietnam and to assess the diagnostic applicability of quantitative real-time PCR assays to diagnose rickettsial diseases. We enrolled 302 patients with acute undifferentiated fever and clinically suspected rickettsiosis during March 2015-March 2017. We used a standardized case report form to collect clinical information and laboratory results at the time of admission and during treatment. We confirmed scrub typhus in 103 (34.1%) patients and murine typhus in 12 (3.3%) patients. These results highlight the need for increased emphasis on training for healthcare providers for earlier recognition, prevention, and treatment of rickettsial diseases in Vietnam.
Assuntos
Tifo por Ácaros/diagnóstico , Tifo por Ácaros/fisiopatologia , Tifo Endêmico Transmitido por Pulgas/diagnóstico , Tifo Endêmico Transmitido por Pulgas/fisiopatologia , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Patologia Molecular , Estudos Prospectivos , Tifo por Ácaros/epidemiologia , Sorotipagem , Tifo Endêmico Transmitido por Pulgas/epidemiologia , VietnãRESUMO
Scrub typhus is an important arthropod-borne disease causing significant acute febrile illness by infection with Orientia spp.Using a risk-based approach, this review examines current practice, the evidence base and regulatory requirements regarding matters of biosafety and biosecurity, and presents the case for reclassification from Risk Group 3 to Risk Group 2 along with recommendations for safe working practices of risk-based activities during the manipulation of Orientia spp. in the laboratory.We recommend to reclassify Orientia spp. to Risk Group 2 based on the classification for RG2 pathogens as being moderate individual risk, low community risk. We recommend that low risk activities, can be performed within a biological safety cabinet located in a Biosafety Level (BSL) 2 core laboratory using standard personal protective equipment. But when the risk assessment indicates, such as high concentration and volume, or aerosol generation, then a higher biocontainment level is warranted. For, the majority of animal activities involving Orientia spp., Animal BSL 2 (ABSL2) is recommended however where high risk activities are performed including necropsies, Animal BSL (ABSL3) is recommended.
Assuntos
Contenção de Riscos Biológicos/classificação , Orientia tsutsugamushi/patogenicidade , Tifo por Ácaros/transmissão , Guias como Assunto , Humanos , Pesquisa , Medição de Risco , Tifo por Ácaros/diagnóstico , Local de TrabalhoRESUMO
This study was done to characterize distribution of Rickettsia spp. in ticks in the northwestern and southwestern provinces in the Republic of Korea. A total of 2,814 ticks were collected between May and September 2009. After pooling, 284 tick DNA samples were screened for a gene of Rickettsia-specific 17-kDa protein using nested PCR (nPCR), and produced 88 nPCR positive samples. Of these positives, 75% contained 190-kDa outer membrane protein gene (ompA), 50% 120-kDa outer membrane protein gene (ompB), and 64.7% gene D (sca4). The nPCR products of ompA, ompB, and sca4 genes revealed close relatedness to Rickettsia japonica, R. heilongjiangensis, and R. monacensis. Most Rickettsia species were detected in Haemaphysalis longicornis. This tick was found a dominant vector of rickettsiae in the study regions in the Republic of Korea.
Assuntos
Rickettsia/classificação , Rickettsia/isolamento & purificação , Carrapatos/microbiologia , Animais , Proteínas da Membrana Bacteriana Externa/genética , Feminino , Masculino , Reação em Cadeia da Polimerase , República da Coreia , Rickettsia/genéticaRESUMO
Orientia tsutsugamushi, an obligate intracellular bacterium that is auxotrophic for the aromatic amino acids and histidine, causes scrub typhus, a potentially deadly infection that threatens 1 billion people. O. tsutsugamushi growth is minimal during the first 24 to 48 h of infection but its growth becomes logarithmic thereafter. How the pathogen modulates cellular functions to support its growth is poorly understood. The unfolded protein response (UPR) is a cytoprotective pathway that relieves endoplasmic reticulum (ER) stress by promoting ER-associated degradation (ERAD) of misfolded proteins. Here, we show that O. tsutsugamushi invokes the UPR in the first 48 h and benefits from ER stress in an amino acid-dependent manner. O. tsutsugamushi also impedes ERAD during this time period. By 72 h, ER stress is alleviated and ERAD proceeds unhindered. Sustained inhibition of ERAD using RNA interference results in an O. tsutsugamushi growth defect at 72 h that can be rescued by amino acid supplementation. Thus, O. tsutsugamushi temporally stalls ERAD until ERAD-derived amino acids are needed to support its growth. The O. tsutsugamushi effector Ank4 is linked to this phenomenon. Ank4 interacts with Bat3, a eukaryotic chaperone that is essential for ERAD, and is transiently expressed by O. tsutsugamushi during the infection period when it inhibits ERAD. Ectopically expressed Ank4 blocks ERAD to phenocopy O. tsutsugamushi infection. Our data reveal a novel mechanism by which an obligate intracellular bacterial pathogen modulates ERAD to satisfy its nutritional virulence requirements.
Assuntos
Degradação Associada com o Retículo Endoplasmático/fisiologia , Orientia tsutsugamushi/fisiologia , Células HeLa , Humanos , Resposta a Proteínas não DobradasRESUMO
While studying rickettsial infections in Peru, we detected Rickettsia asembonensis in fleas from domestic animals. We characterized 5 complete genomic regions (17kDa, gltA, ompA, ompB, and sca4) and conducted multilocus sequence typing and phylogenetic analyses. The molecular isolate from Peru is distinct from the original R. asembonensis strain from Kenya.
Assuntos
DNA Bacteriano/genética , Tipagem de Sequências Multilocus , Rickettsia/genética , Rickettsia/isolamento & purificação , Animais , Peru , Filogenia , Rickettsia/classificação , Sifonápteros/microbiologiaRESUMO
Investigation of a scrub typhus outbreak in Thailand during September 2013 found that 9.1% of Thai soldiers and 11.1% of residents living in areas surrounding training sites had antibodies against the causative agent, Orientia tsutsugamushi. Sequence analysis of O. tsutsugamushi from rodents and chiggers identified 7 genogroups and 3 genotypes.
Assuntos
Surtos de Doenças , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/epidemiologia , Anticorpos Antibacterianos , Humanos , Militares , Infestações por Ácaros/epidemiologia , Tailândia/epidemiologiaRESUMO
Using a large, passive, febrile surveillance program in Iquitos, Peru, we retrospectively tested human blood specimens for scrub typhus group orientiae by ELISA, immunofluorescence assay, and PCR. Of 1,124 participants, 60 (5.3%) were seropositive, and 1 showed evidence of recent active infection. Our serologic data indicate that scrub typhus is present in the Peruvian Amazon.
Assuntos
Tifo por Ácaros/epidemiologia , Humanos , Peru/epidemiologia , Vigilância da População , Estudos Retrospectivos , Tifo por Ácaros/imunologia , Estudos SoroepidemiológicosRESUMO
We developed an intradermal (ID) challenge cynomolgus macaque (Macaca fascicularis) model of scrub typhus, the leading cause of treatable undifferentiated febrile illness in tropical Asia, caused by the obligate intracellular bacterium, Orientia tsutsugamushi. A well-characterized animal model is required for the development of clinically relevant diagnostic assays and evaluation of therapeutic agents and candidate vaccines. We investigated scrub typhus disease pathophysiology and evaluated two O. tsutsugamushi 47-kDa, Ag-based candidate vaccines, a DNA plasmid vaccine (pKarp47), and a virus-vectored vaccine (Kp47/47-Venezuelan equine encephalitis virus replicon particle) for safety, immunogenicity, and efficacy against homologous ID challenge with O. tsutsugamushi Karp. Control cynomolgus macaques developed fever, classic eschars, lymphadenopathy, bacteremia, altered liver function, increased WBC counts, pathogen-specific Ab (IgM and IgG), and cell-mediated immune responses. Vaccinated macaques receiving the DNA plasmid pKarp47 vaccine had significantly increased O. tsutsugamushi-specific, IFN-γ-producing PBMCs (p = 0.04), reduced eschar frequency and bacteremia duration (p ≤ 0.01), delayed bacteremia onset (p < 0.05), reduced circulating bacterial biomass (p = 0.01), and greater reduction of liver transaminase levels (p < 0.03) than controls. This study demonstrates a vaccine-induced immune response capable of conferring sterile immunity against high-dose homologous ID challenge of O. tsutsugamushi in a nonhuman primate model, and it provides insight into cell-mediated immune control of O. tsutsugamushi and dissemination dynamics, highlights the importance of bacteremia indices for evaluation of both natural and vaccine-induced immune responses, and importantly, to our knowledge, has determined the first phenotypic correlates of immune protection in scrub typhus. We conclude that this model is suitable for detailed investigations into vaccine-induced immune responses and correlates of immunity for scrub typhus.
Assuntos
Antígenos de Bactérias/uso terapêutico , Modelos Animais de Doenças , Tifo por Ácaros/prevenção & controle , Vacinação/métodos , Vacinas de DNA/uso terapêutico , Animais , Antígenos de Bactérias/imunologia , Macaca fascicularis , Masculino , Vacinas de DNA/imunologiaRESUMO
We assessed serum samples from 1,000 US Marines deployed to Afghanistan during 2001-2010 to find evidence of 4 rickettsial pathogens. Analysis of predeployment and postdeployment samples showed that 3.4% and 0.5% of the Marines seroconverted for the causative agents of Q fever and spotted fever group rickettsiosis, respectively.
Assuntos
Coxiella burnetii/isolamento & purificação , Militares , Febre Q/microbiologia , Infecções por Rickettsia/microbiologia , Rickettsia , Adolescente , Adulto , Afeganistão/epidemiologia , Anticorpos Antibacterianos/sangue , Humanos , Pessoa de Meia-Idade , Febre Q/sangue , Febre Q/epidemiologia , Infecções por Rickettsia/sangue , Infecções por Rickettsia/epidemiologia , Estudos Soroepidemiológicos , Estados Unidos , Guerra , Adulto JovemRESUMO
To increase knowledge of undifferentiated fevers in Kenya, we tested paired serum samples from febrile children in western Kenya for antibodies against pathogens increasingly recognized to cause febrile illness in Africa. Of patients assessed, 8.9%, 22.4%, 1.1%, and 3.6% had enhanced seroreactivity to Coxiella burnetii, spotted fever group rickettsiae, typhus group rickettsiae, and scrub typhus group orientiae, respectively.
Assuntos
Febre Q/epidemiologia , Infecções por Rickettsia/epidemiologia , Tifo por Ácaros/epidemiologia , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Criança , Pré-Escolar , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Febre/epidemiologia , Febre/microbiologia , História do Século XXI , Humanos , Lactente , Quênia/epidemiologia , Masculino , Febre Q/diagnóstico , Febre Q/história , Febre Q/microbiologia , Infecções por Rickettsia/diagnóstico , Infecções por Rickettsia/história , Infecções por Rickettsia/microbiologia , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/história , Tifo por Ácaros/microbiologia , Estações do AnoRESUMO
The enzyme-linked immunosorbent assay (ELISA) has been proposed as an alternative serologic diagnostic test to the indirect immunofluorescence assay (IFA) for scrub typhus. Here, we systematically determine the optimal sample dilution and cutoff optical density (OD) and estimate the accuracy of IgM ELISA using Bayesian latent class models (LCMs). Data from 135 patients with undifferentiated fever were reevaluated using Bayesian LCMs. Every patient was evaluated for the presence of an eschar and tested with a blood culture for Orientia tsutsugamushi, three different PCR assays, and an IgM IFA. The IgM ELISA was performed for every sample at sample dilutions from 1:100 to 1:102,400 using crude whole-cell antigens of the Karp, Kato, and Gilliam strains of O. tsutsugamushi developed by the Naval Medical Research Center. We used Bayesian LCMs to generate unbiased receiver operating characteristic curves and found that the sample dilution of 1:400 was optimal for the IgM ELISA. With the optimal cutoff OD of 1.474 at a sample dilution of 1:400, the IgM ELISA had a sensitivity of 85.7% (95% credible interval [CrI], 77.4% to 86.7%) and a specificity of 98.1% (95% CrI, 97.2% to 100%) using paired samples. For the ELISA, the OD could be determined objectively and quickly, in contrast to the reading of IFA slides, which was both subjective and labor-intensive. The IgM ELISA for scrub typhus has high diagnostic accuracy and is less subjective than the IgM IFA. We suggest that the IgM ELISA may be used as an alternative reference test to the IgM IFA for the serological diagnosis of scrub typhus.
Assuntos
Anticorpos Antibacterianos/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Imunoglobulina M/sangue , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/diagnóstico , Testes Sorológicos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Tailândia , Adulto JovemRESUMO
A novel rickettsial agent, 'Candidatus Rickettsia asembonensis' strain NMRCiiT, was isolated from cat fleas, Ctenocephalides felis, from Kenya. Genotypic characterization of the new isolate based on sequence analysis of five rickettsial genes, rrs, gltA, ompA, ompB and sca4, indicated that this isolate clustered with Rickettsia felis URRWXCal2. The degree of nucleotide similarity demonstrated that isolate NMRCiiT belongs within the genus Rickettsia and fulfils the criteria for classification as a representative of a novel species. The name Rickettsia asembonensis sp. nov. is proposed, with NMRCiiT (=DSM 100172T=CDC CRIRC RAS001T=ATCC VR-1827T) as the type strain.
Assuntos
Ctenocephalides/microbiologia , Filogenia , Rickettsia/classificação , Animais , Técnicas de Tipagem Bacteriana , Gatos , DNA Bacteriano/genética , Genes Bacterianos , Quênia , RNA Ribossômico 16S/genética , Rickettsia/genética , Rickettsia/isolamento & purificação , Análise de Sequência de DNARESUMO
Serum samples from patients in Kenya with febrile illnesses were screened for antibodies against bacteria that cause spotted fever, typhus, and scrub typhus. Seroprevalence was 10% for spotted fever group, <1% for typhus group, and 5% for scrub typhus group. Results should help clinicians expand their list of differential diagnoses for undifferentiated fevers.
Assuntos
Anticorpos Antibacterianos/imunologia , Orientia tsutsugamushi/imunologia , Infecções por Rickettsia/epidemiologia , Infecções por Rickettsia/imunologia , Rickettsia/imunologia , Tifo por Ácaros/epidemiologia , Tifo por Ácaros/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Criança , Pré-Escolar , Feminino , Febre/epidemiologia , Febre/imunologia , Febre/microbiologia , Humanos , Lactente , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Vigilância da População , Prevalência , Infecções por Rickettsia/transmissão , Tifo por Ácaros/transmissão , Estudos Soroepidemiológicos , Adulto JovemRESUMO
Three novel isolates of the genus Bartonella were recovered from the blood of two patients enrolled in a clinical trial for the treatment of chronic stage Bartonella bacilliformis infection (verruga peruana) in Caraz, Ancash, Peru. The isolates were initially characterized by sequencing a fragment of the gltA gene, and found to be disparate from B. bacilliformis. The isolates were further characterized using phenotypic and genotypic methods, and found to be genetically identical to each other for the genes assessed, but distinct from any known species of the genus Bartonella, including the closest relative B. bacilliformis. Other characteristics of the isolates, including their morphology, microscopic and biochemical properties, and growth patterns, were consistent with members of the genus Bartonella. Based on these results, we conclude that these three isolates are members of a novel species of the genus Bartonella for which we propose the name Bartonella ancashensis sp. nov. (type strain 20.00T = ATCC BAA-2694T = DSM 29364T).