Fever Rickettsiae Research Articles

A Study of Cardiopulmonary Manifestations in Patients with Rickettsial Fever at a Tertiary Care Centre

A Study of Cardiopulmonary Manifestations in Patients with Rickettsial Fever at a Tertiary Care Centre

Scrub Typhus – An Overlooked Aetiology for Acute Febrile Illness in Bangladesh: A Case Report

Rickettsial fevers are a heterogeneous group of illness characterized by fever, headache, myalgia and rash. Rickettsia has a wide global distribution and regional species specificity. In spite of significant serosurveillance reports, rickettsial fevers are occasionally reported in Bangladesh. Here, we report a case of scrub typhus occurring in a young girl who presented with fever and had a typical eschar. We emphasize rickettsial fever should be a differential diagnosis in acute fever without localizing symptoms and signs in Bangladesh.
 Birdem Med J 2019; 9(1): 80-81

A study of clinic- laboratory profile of Rickettsial fever in children at tertiary health care center

A study of clinic- laboratory profile of Rickettsial fever in children at tertiary health care center

Isolated third nerve palsy complicating Rickettsial fever: A rare neurological complication

Isolated third nerve palsy complicating Rickettsial fever: A rare neurological complication

Coma Secondary to Rickettsia typhi

SESSION TITLE: Student/Resident Critical Care SESSION TYPE: Student/Resident Case Report Slide PRESENTED ON: Tuesday, October 31, 2017 at 04:30 PM - 05:30 PM INTRODUCTION: Rickettsia typhi is an obligate intracellular gram-negative organism that is transmitted by fleas. It causes murine typhus, which is often misdiagnosed due to its indolent and non-specific disease course and underestimated incidence, making it a diagnostic challenge (1). CASE PRESENTATION: An indigent male was brought in by ambulance for seizures during the summer. Physical examination was unremarkable except for fever and Glasgow Coma Score (GCS) of 3. He was intubated for airway protection. Laboratory values were significant for leukocytosis, thrombocytopenia, hyponatremia and elevated lactate dehydrogenase (LDH) of 400 units. Lumbar puncture and computed tomography brain were normal. Despite two weeks of empiric antibiotic therapy, cultures remained negative and the patient continued to have persistent fevers with GCS 3. At the end of the two weeks, a rash was discovered and a rickettsia panel was sent. It returned positive for murine typhus. After initiating treatment with doxycycline, patient became more responsive within a day, was liberated from the ventilator by day 4, and subsequently made a full recovery. DISCUSSION: Murine typhus, which is transmitted by Rickettsia typhi, is characterized by a classic triad of fever, rash and headache, but the entire triad is only reported in 35.1% of cases. In a large review of 1756 patients, only 26.1% developed complications, with 121 patients developing pulmonary infiltrates, 69 patients developing central nervous system involvement and 3 patients developing seizures. This finding makes the patient's presentation exceedingly rare. The review also observed a characteristic tetrad of laboratory abnormalities consisting of transaminitis, elevated LDH, a high erythrocyte sedimentation rate, and hypoalbuminemia. The tetrad was followed by thrombocytopenia and hyponatremia, which were also observed in this patient in addition to the tetrad. This case study demonstrates the diagnostic challenge presented to clinicians in a patient with altered mental status. Treatment of choice is empiric coverage with doxycycline, chloramphenicol, or quinolones, which should not be delayed while awaiting diagnostic confirmation (1,2,3). CONCLUSIONS: We present a case of a rare but possibly life threatening murine typhus, which should be kept in the differential for patients with fever and altered mental status. Reference #1: Tsioutis, C et al. (2017). Clinical and laboratory characteristics, epidemiology, and outcomes of murine typhus: A systematic review. Acta Tropica, 166, 16-24. Reference #2: Phongmany, S. et al. (2006). Rickettsial infections and fever, Vientiane, Laos. Emerging infectious diseases, 12(2), 256. Reference #3: Chang, K. et al. (2014). Identification of factors for physicians to facilitate early differential diagnosis of scrub typhus, murine typhus, and Q fever from dengue fever in Taiwan. Journal of Microbiology, Immunology and Infection. DISCLOSURE: The following authors have nothing to disclose: Ki-Yoon Kim, John Kern, Ahmet Baydur, Zea Borok, Terese Hammond No Product/Research Disclosure Information

Infections and the kidney: a tale from the tropics.

Tropical infections are caused by a variety of bacteria, viruses and parasitic organisms across varying geographical regions and are more often reported in adults than in children. Most of the infections are acute, presenting as a febrile illness with involvement of multiple organ systems, including the kidney. The gamut of renal manifestations extends from asymptomatic urinary abnormalities to acute kidney injury and-albeit rarely-chronic kidney disease. Tropical infections can involve the glomerular, tubulointerstitial and vascular compartments of the kidney. Leptospirosis, malaria, dengue, rickettsial fever and schistosomiasis are the most prevalent tropical infections which affect the kidneys of children living in the tropics. In this review we discuss renal involvement in these most prevalent tropical infections.

Spotted fever rickettsiae in wild-living rodents from south-western Poland

BackgroundRickettsiae are obligate intracellular alpha-proteobacteria. They are transmitted via arthropod vectors, which transmit the bacteria between animals and occasionally to humans. So far, much research has been conducted to indicate reservoir hosts for these microorganisms, but our knowledge is still non-exhaustive. Therefore, this survey was undertaken to investigate the presence of Rickettsia spp. in wild-living small rodents from south-western Poland.ResultsIn total, 337 samples (193 from spleen and 144 from blood) obtained from 193 wild-living rodents: Apodemus agrarius, Apodemus flavicollis, and Myodes glareolus were tested by qPCR for Rickettsia spp. based on a fragment of gltA gene. The prevalence of infection was 17.6% (34/193). Subsequently, the positive samples were analysed by conventional PCR targeting the gltA gene fragment. The genus Rickettsia was confirmed by sequence analysis in four samples from the blood. In two blood samples from A. agrarius, the identified pathogen was Rickettsia helvetica. The Rickettsia obtained from A. flavicollis was assigned to Rickettsia felis-like organisms group. One isolate from A. agrarius could be determined only to the genus level.ConclusionsThis study shows the presence of Rickettsia DNA in tissues of wild-living rodents, suggesting some potential role of these animals in temporarily maintaining and spreading the bacteria in enzootic cycles.

Fibroblast growth factor receptor-1 mediates internalization of pathogenic spotted fever rickettsiae into host endothelium.

Rickettsial infections continue to cause serious morbidity and mortality in severe human cases around the world. Host cell adhesion and invasion is an essential requisite for intracellular growth, replication, and subsequent dissemination of pathogenic rickettsiae. Heparan sulfate proteoglycans [HSPGs] facilitate the interactions between fibroblast growth factor(s) and their tyrosine kinase receptors resulting in receptor dimerization/activation and have been implicated in bacterial adhesion to target host cells. In the present study, we have investigated the contributions of fibroblast growth factor receptors [FGFRs] in rickettsial entry into the host cells. Inhibition of HSPGs by heparinase and FGFRs by AZD4547 (a selective small-molecule inhibitor) results in significant reduction in rickettsial internalization into cultured human microvascular endothelial cells (ECs), which represent the primary targets of pathogenic rickettsiae during human infections. Administration of AZD4547 during R. conorii infection in a murine model of endothelial-target spotted fever rickettsiosis also diminishes pulmonary rickettsial burden in comparison to mock-treated controls. Silencing of FGFR1 expression using a small interfering RNA also leads to similar inhibition of R. rickettsii invasion into ECs. Consistent with these findings, R. rickettsii infection of ECs also results in phosphorylation of tyrosine 653/654, suggesting activation of FGFR1. Using isobaric tag for relative and absolute quantitation [iTRAQ]-based proteomics approach, we further demonstrate association of β-peptide of rickettsial outer membrane protein OmpA with FGFR1. Mechanistically, FGFR1 binds to caveolin-1 and mediates bacterial entry via caveolin-1 dependent endocytosis. Together, these results identify host cell FGFR1 and rickettsial OmpA as another novel receptor-ligand pair contributing to the internalization of pathogenic rickettsiae into host endothelial cells and the potential application of FGFR-inhibitor drugs as adjunct therapeutics against spotted fever rickettsioses.

Prevalence and clinical presentation of Rickettsia, Coxiella, Leptospira, Bartonella and chikungunya virus infections among hospital-based febrile patients from December 2008 to November 2009 in Bangladesh

BackgroundWe conducted a study to identify Rickettsia, Coxiella, Leptospira, Bartonella, and Chikungunya virus infections among febrile patients presenting at hospitals in Bangladesh.MethodsWe collected blood samples from patients at six tertiary hospitals from December 2008 to November 2009 and performed laboratory tests at the United States Centers for Disease Control and Prevention (CDC).ResultsOut of 720 enrolled patients, 263 (37%) were infected with Rickettsia; 132 patients had immunofluorescence antibody titer >64 against spotted fever, 63 patients against scrub typhus fever and 10 patients against typhus fever. Ten patients were identified with Coxiella. We isolated Leptospira from two patients and Bartonella from one patient. Ten patients had antibodies against Chikungunya virus. The proportion of patients who died was higher with rickettsial fever (5%) compared to those without a diagnosis of rickettsial infection (2%). None of the patients were initially diagnosed with rickettsial fever.ConclusionsRickettsial infections are frequent yet under-recognized cause of febrile illness in Bangladesh. Clinical guidelines should be revised so that local clinicians can diagnose rickettsial infections and provide appropriate drug treatment.

Spotted fever rickettsiae and tuberculous meningitis dual infection presenting as acute encephalitis syndrome: A fatal case report

Spotted fever rickettsiae and tuberculous meningitis dual infection presenting as acute encephalitis syndrome: A fatal case report

Prevalence of Rickettsia spp. in Ticks and Serological and Clinical Outcomes in Tick-Bitten Individuals in Sweden and on the Åland Islands.

Tick-transmitted diseases are an emerging health problem, and the hard tick Ixodes ricinus is the main vector for Borrelia spp., tick-borne encephalitis virus and most of the spotted fever Rickettsiae in Europe. The aim of the present study was to examine the incidence of rickettsial infection in the southernmost and south central parts of Sweden and the Åland Islands in Finland, the risk of infection in humans and its correlation with a bite of a Rickettsia-infected tick, the self-reported symptoms of rickettsial disease, and the prevalence of co-infection between Rickettsia spp. and Borrelia spp. Persons with a recent tick bite were enrolled through public media and asked to answer a questionnaire, provide a blood sample and bring detached ticks at enlistment and at follow-up three months later. Blood samples were previously analysed for Borrelia spp. antibodies and, for this report, analysed for antibodies to Rickettsia spp. by immunofluorescence and in 16 cases also using Western Blot. Ninety-six (44.0%) of the 218 participants were seropositive for IgG antibodies to Rickettsia spp. Forty (18.3%) of the seropositive participants had increased titres at the follow-up, indicating recent/current infection, while four (1.8%) had titres indicating probable recent/current infection (≥1:256). Of 472 ticks, 39 (8.3%) were Rickettsia sp. positive. Five (31.3%) of 16 participants bitten by a Rickettsia-infected tick seroconverted. Experience of the self-reported symptoms nausea (p = 0.006) and radiating pain (p = 0.041) was more common among those with recent, current or probable infection compared to those who did not seroconvert. Participants who showed seroreactivity or seroconversion to Rickettsia spp. had more symptoms than those who were seronegative. Seven (3.2%) participants showed seroconversion to Borrelia spp., and three (1.4%) of these showed seroconversion to both Rickettsia spp. and Borrelia spp., in accordance with previous studies in Sweden. Symptoms of rickettsial disease were in most of the cases vague and general that were difficult to differentiate from other tick-borne diseases.

Clinical study & laborotory profile of rickettsial fever in children- a study from rural Maharashtra

Introduction: Rickettsial fever has been reported to be endemic in the Himalayan belt, Maharashtra and Karnataka in India among the adult population. Pediatric data on the same is limited in developing countries. Recently, the profile of rickettsial fever has been described in children in South India with similar clinical features. Material Methods: This study was conducted from the patients admitted in our hospital, Ashwini Rural Medical College, Hospital & RC, Solapur, from the month of January 2014 to June 2015.The inclusion criteria were, clinical suspicion & supportive lab evidence – Weil Felix, positive leucocytosis, thrombocytopenia. Results: In our study age of presentation ranged from 6 months to 12 years, with mean age of 7 yrs, there was no statistically significant sex difference. All patients presented with fever & purpuric rash was seen in 82%, altered sensorium was seen in 58 %, seizures were seen 34% & Hepatosplenomegaly was seen in 65 % of cases. Other investigations: In our study CSF examination was done in 25 patients of which 10 had abnormal findings, 6 showed low sugar and 8 high protein. In our study according to the Weil Felix titers, most probable disease would be tick borne spotted fever or epidemic typhus, since no louse infestation (the scalp and body infestation, lymphadenopathy) was seen in any of the patients, and most of them were from rural areas more chances of tick infestation. Conclusions: The diagnosis of rickettsia should always be kept in mind for workup of exanthematous fever. High index of clinical suspicion and good laboratory co- relation are helpful in detection of more no of cases. Early diagnosis and treatment with doxy and chloramphenicol can reduce the hospital stay and cost. Associated mixed infections may mislead diagnosis and are more fatal. Weil Felix test is not diagnostic standard. It should be interpreted in good clinical context, still it is easily available to all & remains good screening test.

Differences in Intracellular Fate of Two Spotted Fever Group Rickettsia in Macrophage-Like Cells.

Spotted fever group (SFG) rickettsiae are recognized as important agents of human tick-borne diseases worldwide, such as Mediterranean spotted fever (Rickettsia conorii) and Rocky Mountain spotted fever (Rickettsia rickettsii). Recent studies in several animal models have provided evidence of non-endothelial parasitism by pathogenic SFG Rickettsia species, suggesting that the interaction of rickettsiae with cells other than the endothelium may play an important role in pathogenesis of rickettsial diseases. These studies raise the hypothesis that the role of macrophages in rickettsial pathogenesis may have been underappreciated. Herein, we evaluated the ability of two SFG rickettsial species, R. conorii (a recognized human pathogen) and Rickettsia montanensis (a non-virulent member of SFG) to proliferate in THP-1 macrophage-like cells, or within non-phagocytic cell lines. Our results demonstrate that R. conorii was able to survive and proliferate in both phagocytic and epithelial cells in vitro. In contrast, R. montanensis was able to grow in non-phagocytic cells, but was drastically compromised in the ability to proliferate within both undifferentiated and PMA-differentiated THP-1 cells. Interestingly, association assays revealed that R. montanensis was defective in binding to THP-1-derived macrophages; however, the invasion of the bacteria that are able to adhere did not appear to be affected. We have also demonstrated that R. montanensis which entered into THP-1-derived macrophages were rapidly destroyed and partially co-localized with LAMP-2 and cathepsin D, two markers of lysosomal compartments. In contrast, R. conorii was present as intact bacteria and free in the cytoplasm in both cell types. These findings suggest that a phenotypic difference between a non-pathogenic and a pathogenic SFG member lies in their respective ability to proliferate in macrophage-like cells, and may provide an explanation as to why certain SFG rickettsial species are not associated with disease in mammals.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Treatment of Acute Liver Failure in Resource-Constrained Settings without Transplantation Facilities Can Be Improved.

Five-year analysis of rickettsial fevers in children in South India: Clinical manifestations and complications.

Rickettsial infections are re-emerging in the Indian subcontinent, especially among children. Understanding geographical and clinical epidemiology will facilitate early diagnosis and management. Children aged <18yrs hospitalized with clinically-diagnosed rickettsial fever were reviewed retrospectively. Frequency distributions and odds ratios were calculated from tabulated data. Among 262 children hospitalized between January 2008-December 2012, median age was five years, and 61% were male children. Hospitalized cases increased steadily every year, with the highest burden (74%) occurring between September and January each year. Mean duration of fever was 11.5 days. Rash was present in 54.2% (142/262) of children, with 37.0% involving palms and soles. Prevalence of malnutrition was high (45% of children were underweight and 28% had stunting). Retinal vasculitis was seen in 13.7% (36/262), and the risk appeared higher in females. Severe complications were seen in 29% (purpura fulminans, 7.6%; meningitis and meningoencephalitis, 28%; septic shock, 1.9%; acute respiratory distress syndrome, 1.1%). Complications were more likely to occur in anemic children. Positive Weil-Felix test results (titers ≥1:160) were seen in 70% of cases. Elevated OX-K titers suggestive of scrub typhus were seen in 80% (147/184). Patients were treated with chloramphenicol (32%) or doxycycline (68%). Overall mortality among hospitalised children was 1.9%. This five-year analysis from southern India shows a high burden and increasing trend of rickettsial infections among children. The occurrence of retinal vasculitis and a high rate of severe complications draw attention to the need for early diagnosis and management of these infections.

Aetiology of Fever of Unknown Origin: One-Year Experience in a Tertiary Care Hospital of Bangladesh

Background: Fever of unknown origin (FUO) is not an uncommon problem in general medical practice. Sometimes extensive investigations fail to reach an aetiological diagnosis; on the other hand, in few cases, fever resolves spontaneously. This study was aimed to evaluate the aetiology of FUO in a tertiary care setting.Methods: This cross-sectional study was done in the Department of Internal Medicine of BIRDEM General Hospital, Dhaka, Bangladesh from July 2012 to June 2013.Results: Among the 33 patients studied (1.23% of total admissions), 22 (66.7%) were male. Mean age of the study population was 40.2±7.9 years. Most patients (84.8%) were diabetic. Infection (20, 60.6%) was the commonest cause, followed by malignancy (9, 27.3%). Among the infective causes (20), extra-pulmonary tuberculosis (5, 25%) was the commonest, followed by liver abscess (4, 20%). Other less common causes were Kala-azar (1), malaria (2), histoplasmosis (2), melioidosis (1), cholecystitis (1), renal abscess (1), rickettsial fever (1), apical dental abscess (1) and infective endocarditis (1). Non-Hodgkin’s lymphoma (6), renal cell carcinoma (2) and hepatocellular carcinoma (1) constituted the malignant causes of FUO in this series. Systemic lupus erythematosus was the aetiology of FUO in 1 case. One case remained undiagnosed and 2 patients left hospital before a definite diagnosis could be made.Conclusion: Extra-pulmonary tuberculosis and non-Hodgkin’s lymphoma were the two most common causes of FUO in this study. Repeated history taking, clinical examinations and careful stepwise investigations can diagnose the aetiolgy in most cases of FUO.Birdem Med J 2016; 6(1): 7-11

Molecular analysis of Crimean-Congo hemorrhagic fever virus and Rickettsia in Hyalomma marginatum ticks removed from patients (Spain) and birds (Spain and Morocco), 2009–2015

Crimean-Congo hemorrhagic fever virus (CCHFV) was detected in Spain in 2010. The presence of CCHFV in Hyalomma marginatum ticks from migratory birds passing through Morocco during the spring migration strengthened the hypothesis of the arrival of infected ticks transported by birds to the Iberian Peninsula. Furthermore, Hyalomma species are vectors of bacterial infections such as spotted fever rickettsioses. CCHFV and Rickettsia were screened in Hyalomma ticks from Spain attached to patients (n=12) and birds (n=149). In addition, Rickettsia was investigated in 52 Hyalomma ticks from Morocco (previously reported as CCHFV-infected). No sample collected in Spain showed an infection with CCHFV. Two ticks removed from patients (16.7%), as well as 47 (31.5%) and 4 (7.7%) from birds, collected in Spain and Morocco respectively, were infected with Rickettsia aeschlimannii. Rickettsia sibirica subsp. mongolitimonae was also found in 2 ticks from birds collected in Spain (1.3%). The risk of CCHFV-infected ticks attached to migratory birds to reach the North of Spain is low. This study corroborates the presence of R. aeschlimannii in Spain and Morocco, and supports that H. marginatum can be a potential vector of R. sibirica subsp. mongolitimonae in the Iberian Peninsula.

Transmission mechanisms of an emerging insect-borne rickettsial pathogen.

BackgroundVector-borne pathogens must overcome arthropod infection and escape barriers (e.g. midgut and salivary glands) during the extrinsic incubation period (EIP) before subsequent transmission to another host. This particular timespan is undetermined for the etiological agent of flea-borne spotted fever (Rickettsia felis). Artificial acquisition of R. felis by blood-feeding cat fleas revealed dissemination to the salivary glands after seven days; however, this length of time is inconsistent with co-feeding studies that produced infectious cat fleas within 24 h of infection. In the current study, we demonstrated that an alternative mechanism is responsible for the early-phase transmission that typifies flea-borne R. felis spread.MethodsCo-feeding transmission bioassays were constructed to assess temporal dynamics of R. felis amongst cat fleas, including exposure time to produce infectious fleas and association time to transmit infection to naïve fleas. Additional experiments examined the proportion of R. felis-exposed cat fleas with contaminated mouthparts, as well as the likelihood for cat fleas to release R. felis from their mouthparts following exposure to an infectious bloodmeal. The potential for mechanical transmission of R. felis by co-feeding cat fleas was further examined using fluorescent latex beads, as opposed to a live pathogen, which would not require a biological mechanism to achieve transmission.ResultsAnalyses revealed that R. felis-infected cat fleas were infectious to naïve fleas less than 24 h after exposure to the pathogen, but showed no rickettsial dissemination to the salivary glands during this early-phase transmission. Additionally, the current study revealed that R. felis-infected cat fleas must co-feed with naïve fleas for more than 12 h in order for early-phase transmission to occur. Further evidence supported that contaminated flea mouthparts may be the source of the bacteria transmitted early, and demonstrated that R. felis is released from the mouthparts during brief probing events. Moreover, the use of fluorescent latex beads supports the notion that early-phase transmission of R. felis is a mechanical mechanism.ConclusionsDetermination of the transmission mechanisms utilized by R. felis is essential to fully understand the vulnerability of susceptible vertebrate hosts, including humans, to this pathogen.

A hospital based survey for rickettsioses in Shimoga, Karnataka using the Weil-Felix test

Background: Members of the genus Rickettsiae are transmitted by ticks, mites and lice to humans. The rickettsial agents are important causes of fever. Clinical diagnosis of rickettsial fevers is difficult and laboratory support is necessary to confirm the etiology. Mortality is 30-40% in untreated cases. The Weil-Felix test has been traditionally used to detect rickettsial antibodies in sera. However, the test has poor sensitivity. Despite availability of newer modalities of diagnosis, many laboratories offer only the Weil-Felix test for diagnosing rickettsial fevers. Objectives: To obtain information about the types of rickettsial fevers present in Shimoga, Karnataka, using the Weil-Felix test. Methods: 277 patients with undiagnosed fever of seven days or more were included in the prospective study. Sera were subjected to a panel of tests to screen for common infectious etiologies including rickettsiae. Only the (exclusively) Weil-Felix positive sera were considered for the study. Serum samples testing positive for any other infectious disease with/ without detectable rickettsial antibodies were not studied further. Results of the Weil-Felix test were analyzed. Results: Of the total 277 samples, 87 (31.4%) were positive for rickettsial antibodies. Spotted fevers (34.50%) and the scrub typhus (25.30%) are the commonest rickettsioses. Typhus fevers are also present (17.25%). Younger males were more frequently seen to have rickettsial fever, but this could be a fallacy. Weil-Felix test could not detect antibodies in 71 (27.8%) clinically suspected rickettsial fever samples. Conclusions: In Shimoga, Karnataka, spotted fever, scrub typhus and typhus fevers are present. The Weil-Felix test despite having limitations remains useful at present. More studies need to be conducted at the community level in Shimoga district, Karnataka to get a clearer picture of the types of rickettsia and the magnitude of the problem. Keywords: Karnataka, Rickettsia, Scrub typhus, Shimoga, S

Итоги и перспективы изучения клещевых трансмиссивных лихорадок (на примере Астраханской риккетсиозной лихорадки)

Итоги и перспективы изучения клещевых трансмиссивных лихорадок (на примере Астраханской риккетсиозной лихорадки)