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Travel Medicine and Infectious Disease 2021The aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d'Ivoire.
BACKGROUND
The aetiologies of fever are poorly understood in sub-Saharan Africa. We aimed to assess the burden of malaria and bacteria in Côte d'Ivoire.
METHODS
Blood samples from 438 febrile and 346 afebrile people were screened using molecular tools.
RESULTS
Plasmodium falciparum was the most common microorganism associated with fever (46.8% in febrile, 23.4% in afebrile people; p < 0.001). Bacteraemia was detected in 21.7% of febrile people and 12.7% of afebrile people (p = 0.001). Streptococcus pneumoniae was the main cause of bacteraemia (7.1% of febrile and 0.6% of afebrile individuals; p < 0.001). Non-typhoidal Salmonella spp. was detected in 4.5% of febrile people and 1.2% of afebrile individuals (p < 0.001). Salmonella enterica Typhi and S. enterica Paratyphi were only detected in febrile subjects (1.4% and 2.1%), as well as Tropheryma whipplei (0.9%), Streptococcus pyogenes (0.7%), and Plasmodium ovale (4.6%). The prevalence in febrile and afebrile people was similar for Staphylococcus aureus (3.6-4.9%), Rickettsia felis (5.5-6.4%), Mansonella perstans (3.0-3.2%), and Plasmodium malariae (1.6-2.3%). Comorbidities were higher in febrile than in afebrile subjects (10.3% versus 5.5%; p = 0.01); 82% involving P. falciparum. All patients co-infected with P. falciparum and S. pneumoniae were febrile whereas 30% of those infected by P. falciparum alone were not (p = 0.02). Among febrile participants, 30.4% with malaria and 54.7% with bacteraemia had received neither antimalarial nor antibiotic therapy.
CONCLUSION
Identification of etiologies of acute febrile diseases in sub-Saharan Africa proposes keys to successful treatment and prevention of infectious diseases. Vaccination campaigns may decrease the morbidity of mono- and co-infections by preventable microorganisms.
Topics: Bacteremia; Cote d'Ivoire; Humans; Malaria; Malaria, Falciparum; Retrospective Studies
PubMed: 34146685
DOI: 10.1016/j.tmaid.2021.102105 -
PloS One 2021Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R....
Rickettsioses are neglected and emerging potentially fatal febrile diseases that are caused by obligate intracellular bacteria, rickettsiae. Rickettsia (R.) typhi and R. prowazekii constitute the typhus group (TG) of rickettsiae and are the causative agents of endemic and epidemic typhus, respectively. We recently generated a monoclonal antibody (BNI52) against R. typhi. Characterization of BNI52 revealed that it specifically recognizes TG rickettsiae but not the members of the spotted fever group (SFG) rickettsiae. We further show that BNI52 binds to protein fragments of ±30 kDa that are exposed on the bacterial surface and also present in the periplasmic space. These protein fragments apparently derive from the cytosolic GroEL protein of R. typhi and are also recognized by antibodies in the sera from patients and infected mice. Furthermore, BNI52 opsonizes the bacteria for the uptake by antigen presenting cells (APC), indicating a contribution of GroEL-specific antibodies to protective immunity. Finally, it is interesting that the GroEL protein belongs to 32 proteins that are differentially downregulated by R. typhi after passage through immunodeficient BALB/c CB17 SCID mice. This could be a hint that the rickettsia GroEL protein may have immunomodulatory properties as shown for the homologous protein from several other bacteria, too. Overall, the results of this study provide evidence that GroEL represents an immunodominant antigen of TG rickettsiae that is recognized by the humoral immune response against these pathogens and that may be interesting as a vaccine candidate. Apart from that, the BNI52 antibody represents a new tool for specific detection of TG rickettsiae in various diagnostic and experimental setups.
Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Antigens, Bacterial; Cell Line; Chaperonin 60; HEK293 Cells; Humans; Mice, Inbred BALB C; Mice, SCID; Periplasm; Rickettsia Infections; Rickettsia typhi; Xenopus laevis; Mice
PubMed: 34111210
DOI: 10.1371/journal.pone.0253084 -
MSphere May 2021Species of (: ) are obligate intracellular parasites of a wide range of eukaryotes, with recognized arthropod-borne human pathogens belonging to the transitional group...
Species of (: ) are obligate intracellular parasites of a wide range of eukaryotes, with recognized arthropod-borne human pathogens belonging to the transitional group (TRG), typhus group (TG), and spotted fever group (SFG) rickettsiae. Growing in the host cytosol, rickettsiae pilfer numerous metabolites to make a typical Gram-negative bacterial cell envelope. The O-antigen of rickettsial lipopolysaccharide (LPS) is immunogenic and has been shown to tether the S-layer to the rickettsial surface; however, little is known about the structure and immunogenicity of the lipid A moiety. The structure of lipid A, the membrane anchor of LPS, affects the ability of this molecule to interact with components of the host innate immune system, specifically the MD-2/TLR4 receptor complex. To dissect the host responses that can occur during and infection, structural analysis of lipid A is needed. Lipid A was extracted from four species and structurally analyzed. (TRG), (TG), and (SFG) produced a similar structure, whereas (SFG) altered the length of a secondary acyl group. While all structures have longer acyl chains than known highly inflammatory hexa-acylated lipid A structures, the modification should differentially alter interactions with the hydrophobic internal pocket in MD2. The significance of these characteristics toward inflammatory potential as well as membrane dynamics between arthropod and vertebrate cellular environments warrants further investigation. Our work adds lipid A to the secretome and O-antigen as variable factors possibly correlating with phenotypically diverse rickettsioses. Spikes in rickettsioses occur as deforestation, urbanization, and homelessness increase human exposure to blood-feeding arthropods. Still, effective vaccines remain elusive. Recent studies have determined that lipopolysaccharide anchors the protective S-layer to the bacterial surface and elicits bactericidal antibodies. Furthermore, growing immunological evidence suggests vertebrate sensors (MD-2/TLR4 and noncanonical inflammasome) typically triggered by the lipid A portion of lipopolysaccharide are activated during infection. However, the immunopotency of lipid A is unknown due to poor appreciation for its structure. We determined lipid A structures for four distinct rickettsiae, revealing longer acyl chains relative to highly inflammatory bacterial lipid A. Surprisingly, lipid A of the Rocky Mountain spotted fever agent deviates in structure from other rickettsiae. Thus, lipid A divergence may contribute to variable disease phenotypes, sounding an alarm for determining its immunopotency and possible utility (i.e., as an adjuvant or anti-inflammatory) for development of more prudent rickettsiacidal therapies.
Topics: Humans; Lipid A; Rickettsia; Rickettsia Infections
PubMed: 33952661
DOI: 10.1128/mSphere.00184-21 -
The American Journal of Tropical... Apr 2021Undifferentiated febrile illness still represents a demanding medical problem all over the world, but primarily in low- and middle-income countries. Scientific and...
Undifferentiated febrile illness still represents a demanding medical problem all over the world, but primarily in low- and middle-income countries. Scientific and clinical investigations related to undifferentiated febrile illness and rickettsial diseases in Kazakhstan are lacking. This study reflects the investigation of antibodies against spotted fever group (SFG) and typhus group (TG) rickettsiae in patients with undifferentiated febrile illness in the southern region of Kazakhstan (Almaty and Kyzylorda oblasts). Paired serum samples were gathered from 13 hospitals in these two oblasts and explored for the presence of IgM and IgG antibodies against typhus group and IgG antibodies against spotted fever group rickettsiae using ELISA. Patient's questionnaires were statistically analyzed. In total, 802 inpatients from Almaty (N = 9) and Kyzylorda (N = 4) hospitals were included in this research. Based on ELISA results, 250 patients out of 802 (31.2%) from both oblasts had IgG antibodies against SFG rickettsiae. Results from 11 (1.4%) patients indicated acute infection with tick-borne rickettsiosis. Regarding TG rickettsiae (R. typhi), a past infection was detected in 248 (30.9%) febrile patients and acute infection in 22 (2.7%) patients in the two selected oblasts. The data indicated that SFG and TG rickettsioses are present in Kazakhstan. Kazakh physicians should be aware of these emerging diseases in both investigated oblasts because the occurrence of these diseases is not suspected during day-to-day clinical practice. The identification of rickettsial pathogens and implementation of modern laboratory methods for the diagnostics of rickettsioses are in need throughout Kazakhstan.
Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Enzyme-Linked Immunosorbent Assay; Female; Fever; Hospitalization; Humans; Immunoglobulin G; Kazakhstan; Male; Middle Aged; Rickettsia; Rickettsia Infections; Tick-Borne Diseases; Young Adult
PubMed: 33901004
DOI: 10.4269/ajtmh.20-0388 -
Comparative Immunology, Microbiology... Jun 2021In this study, we assessed the presence of vector-borne microorganisms in different species of fleas collected from different hosts in diverse areas of South-Western...
In this study, we assessed the presence of vector-borne microorganisms in different species of fleas collected from different hosts in diverse areas of South-Western Europe by molecular methods. A total of 319 fleas belonging to eight different species was tested for the presence of eight microorganisms. Wolbachia spp. endosymbionts were detected in Ctenocephalides felis, Pulex irritans, Archaeopsylla erinacei and Ctenophthalmus baeticus boisseauorum specimens. Rickettsia felis, an emerging pathogen, was detected in C. felis, A. erinacei and Ct. b. boisseauorum. Rickettsia typhi, the agent of murine typhus was detected for the first time in A. erinacei and Mycobacterium spp. were detected for the first time in fleas (C. felis, P. irritans and A. erinacei). Lastly, five different species of Bartonella were detected in fleas' DNA in this study, including a possible new bacterium belonging to this genus. With this study, we updated the knowledge of the flea-borne bacteria present in the South-West of Europe reinforcing the idea about the necessity to expand and increase the current knowledge on flea-borne pathogens.
Topics: Animals; Bacteria; Ctenocephalides; Europe; Flea Infestations; France; Siphonaptera; Spain
PubMed: 33895462
DOI: 10.1016/j.cimid.2021.101648 -
PLoS Neglected Tropical Diseases Apr 2021Current knowledge on Rickettsia felis infection in humans is based on sporadic case reports. Here we conducted a retrospective seroepidemiological survey of R. felis...
BACKGROUND
Current knowledge on Rickettsia felis infection in humans is based on sporadic case reports. Here we conducted a retrospective seroepidemiological survey of R. felis infection among febrile patients visiting a medical center in Taipei.
METHODOLOGY/PRINCIPAL FINDINGS
A total of 122 patients with suspected rickettsioses presenting with fever of unknown origin (FUO) but tested negative for scrub typhus, murine typhus, or Q fever were retrospectively identified during 2009 to 2010. The archived serum samples were examined for the presence of antibodies against R. felis, Rickettsia japonica, and Rickettsia typhi using microimmunofluorescence (MIF) assay. Serological evidence of Rickettsia exposure was found in 23 (19%, 23/122) patients. Eight patients had antibodies reactive to R. felis, including four with current infection (a ≥4-fold increase in IgG titer between acute and convalescent sera). The clinical presentations of these four patients included fever, skin rash, lymphadenopathy, as well as more severe conditions such as pancytopenia, hepatomegaly, elevated liver enzymes/bilirubin, and life-threatening acute respiratory distress syndrome. One of the patients died after doxycycline was stopped after being tested negative for scrub typhus, Q fever, and murine typhus.
CONCLUSIONS
Rickettsia felis is a neglected flea-borne pathogen in Taiwan, and its infection can be life-threatening. Further prospective studies of the prevalence of R. felis among patients with FUO and compatible clinical manifestations are warranted.
Topics: Adolescent; Adult; Aged; Animals; Female; Humans; Male; Mice; Middle Aged; Retrospective Studies; Rickettsia; Rickettsia Infections; Rickettsia felis; Rickettsia typhi; Risk Factors; Seroepidemiologic Studies; Taiwan; Typhus, Endemic Flea-Borne; Young Adult
PubMed: 33872325
DOI: 10.1371/journal.pntd.0009355 -
Military Medicine Jul 2022Leptospirosis and rickettsial diseases are global zoonotic diseases. In severe infection cases, mortality can range from 10% to 30%. Currently most epidemiological data...
INTRODUCTION
Leptospirosis and rickettsial diseases are global zoonotic diseases. In severe infection cases, mortality can range from 10% to 30%. Currently most epidemiological data available are based on outbreak investigations and hospital-based studies from endemic countries. The U.S. soldiers at military bases in these countries are highly vulnerable due to the fact that most of them are immunologically naïve to these pathogens. No risk assessment of leptospirosis and rickettsial diseases among U.S. military personnel in Honduras is currently available. This study was aimed at determining the prevalence of leptospirosis and rickettsial diseases in U.S. military personnel deployed to Honduras using serological assays.
MATERIALS AND METHODS
A cohort of pre- and post-deployment sera from the most recent 1,000 military personnel stationed in Honduras for at least 6 months between 2000 and 2016 was identified for this study. Serum specimens from these eligible subjects were retrieved. All post-deployment serum specimens were screened at a dilution of 1:100 for the presence of IgG antibodies to Leptospira and Rickettsia pathogens. The pre-deployment sera from those individuals with post-deployment IgG antibodies above cutoff (i.e., seropositive) were tested to determine seroconversion. Seroconversion was defined as conversion of an optical density value from below the cutoff (i.e., negative) in a pre-deployed specimen to above the cutoff (i.e., positive) in a post-deployed specimen at a titer of 100.
RESULTS
The seropositive post-deployment specimens for antibodies against Leptospira (causing leptospirosis), Rickettsia typhi (causing murine typhus [MT]), spotted fever group rickettsioses (SFGR, causing SFG Rickettsia), Orientia tsutsugamushi (causing scrub typhus [ST]), and Coxiella burnetii (causing Q fever [QF]) were 11.6%, 11.3%, 6%, 5.6%, and 8.0%, respectively. The seroconverted rate in those assigned to Honduras from 2000 to 2016 was 7.3%, 1.9%, 3.9%, 4.3%, and 2.7% for leptospirosis, MT, SFGR, ST, and QF, respectively. Among the seroconverted specimens, 27 showed seroconversion of at least two antibodies. These seroconverted individuals accounted for 8.8% (3 out of 34) of the personnel who looked for medical attention during their deployment.
CONCLUSIONS
Our results suggest a leptospirosis seroconversion rate of 7.3%, which is higher than the 0.9% and 3.9% seroconversion in Korea and Japan, respectively. The higher rate of seroconversion indicates potential risk of Leptospira exposure. Additional testing of water samples in the pools and pits around the training sites to locate the infected areas is important to eliminate or reduce future exposure to Leptospira during trainings. The rates of seroconversion for ST, MT, spotted fever Rickettsia, and QF were 4.3%, 1.9%, 3.9%, and 2.7%, respectively, indicating the potential exposure to a variety of rickettsial-related pathogens. Testing of vectors for rickettsial pathogens in the areas could inform effective vector control countermeasures to prevent exposure. Proper precaution and protective measures are needed to better protect military personnel deployed to Honduras.
Topics: Animals; Antibodies, Bacterial; Honduras; Humans; Immunoglobulin G; Leptospira; Leptospirosis; Mice; Military Personnel; Rickettsia Infections; Scrub Typhus; Typhus, Endemic Flea-Borne
PubMed: 33861353
DOI: 10.1093/milmed/usab120 -
Journal of Ophthalmic Inflammation and... Mar 2021To report a case of abducens nerve palsy with associated retinal involvement due to rickettsia typhi infection.
OBJECTIVE
To report a case of abducens nerve palsy with associated retinal involvement due to rickettsia typhi infection.
MATERIAL AND METHODS
A single case report documented with multimodal imaging.
RESULTS
A 18-year-old woman with a history of high-grade fever was initially diagnosed with typhoid fever and treated with fluoroquinolone. She presented with a 5-day history of diplopia and headaches. Her best-corrected visual acuity was 20/20 in both eyes. Ocular motility examination showed left lateral gaze restriction. Lancaster test confirmed the presence of left abducens palsy. Fundus examination showed optic disc swelling in both eyes associated with superotemporal retinal hemorrhage and a small retinal infiltrate with retinal hemorrhage in the nasal periphery in the left eye. Magnetic resonance imaging (MRI) of the brain and orbits showed no abnormalities. A diagnosis of rickettsial disease was suspected and the serologic test for Richettsia Typhi was positive. The patient was treated with doxycycline (100 mg every 12 h) for 15 days with complete recovery of the left lateral rectus motility and resolution of optic disc swelling, retinal hemorrhages, and retinal infiltrate.
CONCLUSION
Rickettsial disease should be considered in the differential diagnosis of abducens nerve palsy in any patient with unexplained fever from endemic area. Fundus examination may help establish an early diagnosis and to start an appropriate rickettsial treatment.
PubMed: 33748920
DOI: 10.1186/s12348-021-00239-1 -
PLoS Neglected Tropical Diseases Mar 2021There are few studies about the presence of murine typhus in Greece. Our objective was to conduct a large scale retrospective investigation to determine the clinical and...
BACKGROUND
There are few studies about the presence of murine typhus in Greece. Our objective was to conduct a large scale retrospective investigation to determine the clinical and epidemiological features of patients diagnosed with murine typhus in Greece.
METHODOLOGY/PRINCIPAL FINDINGS
From 2012 to 2019 serum samples from hospitalized patients and outpatients throughout Greece suspected for murine typhus infection were tested by immunofluorescence assay for Rickettsia typhi. Immunofluorescence positive samples obtained since 2016 were also tested by qPCR targeting R. typhi. Clinical and epidemiological data were retrospectively collected for the patients with confirmed murine typhus. Overall, we tested 5,365 different patients and, in total, 174 patients from all geographic regions of Greece were diagnosed with murine typhus. The most frequently reported sign or symptom was fever (89%), followed by headache (84%) and rash (81%). The classical triad of fever, headache, and rash was present in 72% of patients during their illness. Severe infections with complications including acute renal failure or septic shock were not recorded. The majority of cases (81%) occurred during May-October and peaked in June and September. Most of patients (81%) infected in Athens, recalled that their only activity the last weeks before symptoms onset was swimming on the beach and 59% of them also reported an insect bite while sunbathing.
CONCLUSIONS/SIGNIFICANCE
Our results may reflect the reemergence of murine typhus in Greece and we highlight the importance of awareness of this difficult-to-recognize undifferentiated febrile illness.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Fluorescent Antibody Technique, Indirect; Greece; Humans; Infant; Insect Bites and Stings; Male; Middle Aged; Real-Time Polymerase Chain Reaction; Retrospective Studies; Rickettsia typhi; Risk Factors; Seasons; Sunbathing; Typhus, Endemic Flea-Borne
PubMed: 33711035
DOI: 10.1371/journal.pntd.0009186 -
Pathogens (Basel, Switzerland) Feb 2021Murine typhus is a flea-borne disease of worldwide distribution with a recent reemergence in the United States of America. There are limited data about the presentation,...
Murine typhus is a flea-borne disease of worldwide distribution with a recent reemergence in the United States of America. There are limited data about the presentation, treatment, and outcomes in the pregnant population. We report on two cases of murine typhus during pregnancy and review the literature to compile previously reported cases. A comprehensive search was performed via the PubMed database for published articles between 1990 and 2020. Seven articles met the criteria of symptomatic pregnant murine typhus infection. A total of 37 patients were identified. Patients frequently presented with a prolonged duration of fevers prior to presentation, headache, and elevated hepatic transaminases. The diagnosis was predominantly based on serology. Treatment varied. Overall, the pregnancy outcome was favorable. Murine typhus can mimic other pregnancy-related pathologies. More exclusive and large-scale studies are needed to learn more of murine typhus during pregnancy.
PubMed: 33670581
DOI: 10.3390/pathogens10020219