Search Results (26)

Introduction: Spotted fever group (SFG) rickettsioses are tick-transmitted infections caused by Gram-negative, obligately intracellular bacteria in the genus Rickettsia. They present as an acute undifferentiated febrile illness, and they are often accompanied by rash and/or eschar. Although the rash of SFG rickettsioses usually consists of macules and papules, some, like in Rickettsia parkeri rickettsiosis, can also manifest with papulovesicular or pustular lesions. Case: We herein present a case of SFG rickettsiosis, due to R. parkeri, that masqueraded as Sweet syndrome (the prototype neutrophilic dermatosis) after the initial results of a shave biopsy. Further investigation of the biopsy specimen by immunohistochemical and PCR analysis would eventually confirm SFG rickettsiosis, with R. parkeri being detected by real-time PCR. Discussion:Rickettsia parkeri is transmitted by the Gulf Coast tick (Amblyomma maculatum) and is an increasingly recognized cause of SFG rickettsiosis in the United States. Rickettsia parkeri should be considered in those with an acute undifferentiated febrile illness with lesions that are pustular or papulovesicular, as prompt recognition and empirical administration of doxycycline results in the rapid resolution of symptoms. Full article

Rickettsioses, often underreported, pose public health challenges. Rickettsia asembonensis is a potential emerging pathogen that was previously detected in humans, animals, and a variety of arthropods. While its pathogenicity in humans remains unclear, it poses a potential public health threat. Here, we present an extended epidemiological, diagnostic, and genetic analysis of the information provided in a preliminary report on the investigation of rickettsiae in Peru. In particular, we report the detection of R. asembonensis in blood specimens collected from four human patients with an acute undifferentiated fever of a seven- to nine-day duration, all of whom tested negative for other vector-borne pathogens. Additionally, we describe the replicative capacity of the R. asembonensis isolates in cell cultures. Full article

The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93–97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness. Full article

Rickettsial diseases (RD) are widely reported all over the world. Scrub typhus (ST) is a major tropical infection which is well documented all over India. Therefore, the index of suspicion of scrub typhus is high among physicians with regard to patients presenting with acute febrile illness (AFI) and acute undifferentiated febrile illness (AUFI) in India. Rickettsial diseases other than ST (non-ST RDs), which include spotted fever group (SFG) rickettsioses and typhus group (TG) rickettsioses are not uncommon in India, but the index of suspicion is not as high as ST unless there is a history of the presence of fever with rashes and/or recent arthropod bites. This review aims to look into the Indian scenario on the epidemiology of non-ST RDs, especially the SFG and TG rickettsioses based on various investigations, spectrum of clinical presentation, challenges and gaps in knowledge to suspect and diagnose these infections. Full article

Fever is a common presentation to urgent-care services and is linked to multiple disease processes. To rapidly determine the etiology of fever, improved diagnostic modalities are necessary. This prospective study of 100 hospitalized febrile patients included both positive (FP) and negative (FN) subjects in terms of infection status and 22 healthy controls (HC). We evaluated the performance of a novel PCR-based assay measuring five host mRNA transcripts directly from whole blood to differentiate infectious versus non-infectious febrile syndromes as compared to traditional pathogen-based microbiology results. The FP and FN groups observed a robust network structure with a significant correlation between the five genes. There were statistically significant associations between positive infection status and four of the five genes: IRF-9 (OR = 1.750, 95% CI = 1.16–2.638), ITGAM (OR = 1.533, 95% CI = 1.047–2.244), PSTPIP2 (OR = 2.191, 95% CI = 1.293–3.711), and RUNX1 (OR = 1.974, 95% CI = 1.069–3.646). We developed a classifier model to classify study participants based on these five genes and other variables of interest to assess the discriminatory power of the genes. The classifier model correctly classified more than 80% of the participants into their respective groups, i.e., FP or FN. The GeneXpert prototype holds promise for guiding rapid clinical decision-making, reducing healthcare costs, and improving outcomes in undifferentiated febrile patients presenting for urgent evaluation. Full article

Scrub typhus is a mite-borne disease caused by a Gram-negative obligately intracellular bacillus, Orientia tsutsugamushi. The disease is endemic in the Asia–Australia–Pacific region, including Thailand. Scrub typhus generally manifests as acute undifferentiated febrile fever along with myalgia, rash, and lymphadenopathy. An eschar can be a valuable diagnostic clue, but this skin lesion may be missed in some patients. The disease symptoms resemble those of other febrile illnesses such as leptospirosis, typhoid, murine typhus, malaria, and dengue fever, making a laboratory diagnosis necessary for the definitive diagnosis. In this study, we expressed a recombinant protein derived from 56-kDa type-specific antigen of O. tsutsugamushi Karp serotype and tested its ability to detect and differentiate scrub typhus infection. IgM and IgG antibodies were determined in sera from scrub typhus (n = 92) and other febrile illness patients (murine typhus (n = 25), melioidosis (n = 36), leptospirosis (n = 42), and dengue (n = 35)) from Thailand. Sensitivities of 87.0% and 59.8% with a specified assay cut-off were obtained for IgM and IgG indirect ELISAs, respectively, with a specificity of 100% in both tests. The sensitivity was increased to 95.7% when a combination of IgM and IgG ELISAs results was considered. Our study suggested a potential of the 56-kDa recombinant protein for further development and evaluation for use in scrub typhus serodiagnosis. Full article

Cardiac undifferentiated pleomorphic sarcoma (UPS) associated with fever and inflammatory response is an extremely rare condition. Herein, we report a rare case of cardiac UPS with unusual clinical presentation and inflammatory response. A 67-year-old male complaining of progressive dyspnea and intermittent fever of unknown cause was referred to our hospital for surgical resection of a left atrial mass. Laboratory analysis showed leukocytosis (26 × 10³/μL) and high C-reactive protein (CRP) levels (155.4 mg/L). Hemoculture tests and urine analysis were negative for infection. A contrast chest computed tomography revealed a mass measuring 5.5 × 4.5 cm, occupying the left atrium cavity. The patient underwent surgical excision of the mass, however, surgical margin of the resected tumor could not be evaluated, due to the multifragmented nature of the resection specimen. Postoperative CRP and leukocyte levels normalized, highlighting the relationship between the tumor and the inflammatory status. Early diagnosis is crucial for a proper management and favorable outcome, enabling patients to undergo chemotherapy and achieve complete surgical resection. Full article

Serology remains a useful indirect method of diagnosing tropical diseases, especially in dengue infection. However, the current literature regarding cross-reactivity between SARS-CoV-2 and dengue serology is limited and revealed conflicting results. As a means to uncover relevant serological insight involving antibody classes against SARS-CoV-2 and cross-reactivity, anti-SARS-CoV-2 IgA, IgM, and IgG ELISA, based on spike and nucleocapsid proteins, were selected for a fever-presenting tropical disease patient investigation. The study was conducted at the Faculty of Tropical Medicine during March to December 2021. The study data source comprised (i) 170 non-COVID-19 sera from 140 adults and children presenting with acute undifferentiated febrile illness and 30 healthy volunteers, and (ii) 31 COVID-19 sera from 17 RT-PCR-confirmed COVID-19 patients. Among 170 non-COVID-19 samples, 27 were false positives (15.9%), of which IgA, IgM, and IgG cross-reactive antibody classes were detected in 18 (10.6%), 9 (5.3%), and 3 (1.8%) cases, respectively. Interestingly, one case exhibited both IgA and IgM false positivity, while two cases exhibited both IgA and IgG false positivity. The false positivity rate in anti-SARS-CoV-2 IgA and IgM was reported in adults with dengue infection (11.3% and 5%) and adults with other tropical diseases (16.7% and 13.3%). The urea dissociation method applied to mitigate false positivity resulted in significantly decreased ELISA-based false and true positives. In conclusion, the analysis of antibody against SARS-CoV-2 in sera of patients with different tropical diseases showed that high IgA and IgM false positivity thus potentially limits serological assay utility in fever-presenting patients in tropical areas. Full article

Febrile illness is a common cause of hospital admission in developing countries, including Bhutan. Prolonged fever admission can add considerable strain on healthcare service delivery. Therefore, identifying the underlying cause of prolonged hospital stays can improve the quality of patient care by providing appropriate empirical treatment. Thus, the study’s aims were to evaluate the aetiologies and factors of prolonged fever admission in Samtse Hospital, Bhutan. Fever admission data from 1 January to 31 December 2020 were retrieved from the Samtse Hospital database. Prolonged hospital stay was defined as those with >5 days of hospital admission. Univariable and multivariable logistic regression was used to identify risk factors for a prolonged hospital stay. Of 290 records, 135 (46.6%) were children (≤12 years), 167 (57.6%) were males, and 237 (81.7%) patients were from rural areas. The common aetiologies for fever admissions were respiratory tract infection (85, 29.3%) and acute undifferentiated febrile illness (48, 16.6%). The prolonged stay was reported in 87 (30.0%) patients. Patients from rural areas (adjusted odds ratio [AOR] = 4.02, 95% CI = 1.58–10.24) and those with respiratory tract infections (AOR = 5.30, 95% CI = 1.11–25.39) and urinary tract infections and kidney disease (AOR = 8.16, 95% CI = 1.33–49.96) had higher odds of prolonged hospital stay. This epidemiological knowledge on prolonged hospital stay can be used by the physician for the management of fever admission in Samtse Hospital. Full article

In Vietnam, the public health burden of rickettsial infections continues to be underestimated due to knowledge gaps in the epidemiology of these diseases. We conducted a systematic study among 27 hospitals from 26 provinces in eight ecological regions throughout Vietnam to investigate the prevalence, distribution, and clinical characteristics of rickettsial diseases. We recruited 1834 patients in the study from April 2018 to October 2019. The findings showed that rickettsial diseases were common among undifferentiated febrile patients, with 564 (30.8%) patients positive by qPCR for scrub typhus, murine typhus or spotted fever. Scrub typhus (484, 85.8%) was the most common rickettsial disease, followed by murine typhus (67, 11.9%) and spotted fever (10, 1.8%). Rickettsial diseases were widely distributed in all regions of Vietnam and presented with nonspecific clinical manifestations. Full article

A point-of-care diagnostic for early and rapid diagnosis of scrub typhus caused by Orientia tsutsugamushi is required for prompt and proper treatment of patients presenting with undifferentiated febrile illnesses. In this study, an immunochromatographic antigen detection test kit (ICT AgTK) that targets the highly conserved O. tsutsugamushi 60 kDa GroEL chaperonin (heat shock protein 60) was developed. E. coli-derived recombinant GroEL expressed from DNA coding for the consensus sequence of 32 GroEL gene sequences extracted from the GenBank database was used to immunize rabbits and mice. Rabbit polyclonal antibodies (pAb) were used for preparing a gold-pAb conjugate, and the rGroEL-specific mouse monoclonal antibody was used as the antigen detection reagent at the ICT test line. In-house validation revealed that the ICT AgTK gave 85, 100 and 95% diagnostic sensitivity, specificity and accuracy, respectively, compared to the combined clinical features and standard IFA when tested on 40 frozen serum samples. The test kits correctly identified 10 scrub typhus samples out of 15 fresh plasma/buffy coat samples of patients with febrile illnesses. For independent laboratory validation, the ICT AgTK was sent to one provincial hospital. The ICT AgTK utilized by the hospital medical technologist correctly identified six scrub typhus samples out of 20 serum samples of patients with fever, as confirmed by specific IgM/IgG detection by IFA. The ICT AgTK is easy to perform with rapid turn-around time. It has the potential to be used as an important tool for on-site and early scrub typhus diagnosis by allowing testing of freshly collected samples (serum, plasma or buffy coat), especially in resource-limited healthcare settings. Full article

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is primarily responsible for coronavirus disease (COVID-19) and it is characterized by respiratory illness with fever and dyspnea. Severe vascular problems and several other manifestations, including neurological ones, have also been frequently reported, particularly in the great majority of “long hauler” patients. SARS-CoV-2 infects and replicates in lung epithelial cells, while dysfunction of endothelial and neuronal brain cells has been observed in the absence of productive infection. It has been shown that the Spike protein can interact with specific cellular receptors, supporting both viral entry and cellular dysfunction. It is thus clear that understanding how and when these receptors are regulated, as well as how much they are expressed would help in unveiling the multifaceted aspects of this disease. Here, we show that SH-SY5Y neuroblastoma cells express three important cellular surface molecules that interact with the Spike protein, namely ACE2, TMPRSS2, and NRP1. Their levels increase when cells are treated with retinoic acid (RA), a commonly used agent known to promote differentiation. This increase matched the higher levels of receptors observed on HUVEC (primary human umbilical vein endothelial cells). We also show by confocal imaging that replication-defective pseudoviruses carrying the SARS-CoV-2 Spike protein can infect differentiated and undifferentiated SH-SY5Y, and HUVEC cells, although with different efficiencies. Neuronal cells and endothelial cells are potential targets for SARS-CoV-2 infection and the interaction of the Spike viral protein with these cells may cause their dysregulation. Characterizing RNA and protein expression tempo, mode, and levels of different SARS-CoV-2 receptors on both cell subpopulations may have clinical relevance for the diagnosis and treatment of COVID-19-infected subjects, including long hauler patients with neurological manifestations. Full article

Dengue (DEN) is the most important human arboviral disease worldwide. Sporadic outbreaks of DEN have been reported since 1980 in urban communities located along the border in southeast Texas and northern Mexico. Other than the Rio Grande Valley region of TX, autochthonous transmission of DENV has not been reported from any other US border communities. As part of a surveillance program for arthropod-borne viruses in Ciudad Juarez, Mexico, during November 2015, a blood sample was obtained from a female patient who experienced an undifferentiated fever and arthralgia. The plasma of the sample was tested for virus in Vero-76 and C6/36 cells. DENV serotype 1 (DENV-1) was isolated in the C6/36 cells, and nucleotide sequencing of the envelope gene and full genome grouped the DENV-1 isolate in the Central America clade. The patient had not traveled outside of Ciudad Juarez, Mexico, thus suggesting DENV-1 infection was acquired in this community. Full article

Syndrome of undifferentiated recurrent fever (SURF) is a heterogeneous group of autoinflammatory diseases (AID) characterized by self-limiting episodes of systemic inflammation without a confirmed molecular diagnosis, not fulfilling the criteria for periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. In this review, we focused on the studies enrolling patients suspected of AID and genotyped them with next generation sequencing technologies in order to describe the clinical manifestations and treatment response of published cohorts of patients with SURF. We also propose a preliminary set of indications for the clinical suspicion of SURF that could help in everyday clinical practice. Full article

Undifferentiated pleomorphic sarcoma (UPS) is major type of soft tissue sarcomas. UPS presenting with inflammation is rare, and its pathophysiology remains unclear. Herein, we report a rare case of UPS with prolonged fever. A 91-year-old female complaining of high fever was referred to our hospital because of a high C-reactive protein (CRP) level of 12.51 mg/dL. She had been experiencing intermittent fevers for approximately 10 years. The fever of unknown origin worsened with time and went into remission with repeated antimicrobial therapy. She also had a mass on her central lower back over the sacral region for 6 years, which showed a gradual increase in size. The blood tests showed that the leukocyte count and neutrophils were 6.51 × 10³ /µL and 70.3%, respectively. She had a 10 × 10 cm mass on her buttock that showed 2-[fluorine-18] fluoro-2-deoxy-d-glucose (FDG) accumulation on FDG-positron emission tomography-computed tomography examination (standardized uptake value-max value: 5.4). A blood culture examination was performed to rule out bacteremia, however, no bacteria were identified. We then performed a needle biopsy and confirmed the diagnosis of UPS; subsequently, the patient underwent a wide-margin resection. A few days after the surgery, her CRP, leukocyte, and neutrophil levels decreased to 0.305 mg/dL, 2.83 × 10³/uL, and 50.1%, respectively. This case demonstrated that UPS with inflammation should be treated surgically as soon as possible after ruling out other sources of infection to achieve a favorable prognosis. Full article