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Medicine Jun 2024Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system... (Review)
Review
RATIONALE
Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon.
PATIENT CONCERNS
A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation.
DIAGNOSES
The patient was diagnosed with a central nervous system infection.
INTERVENTIONS
Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders.
OUTCOMES
Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided.
CONCLUSIONS
The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective.
LESSION
Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.
Topics: Humans; Scrub Typhus; Male; Adolescent; Anti-Bacterial Agents; Doxycycline; Orientia tsutsugamushi; Meningitis, Bacterial
PubMed: 38905360
DOI: 10.1097/MD.0000000000038613 -
PLoS Biology Jun 2024Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host...
Candida albicans is a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulating C. albicans biofilm formation, we performed a large-scale screen with 2,454 C. albicans doxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of the ZCF15 and ZCF26 paralogs that encode transcription factors and have orthologs only in biofilm-forming species of the Candida clade, caused impaired biofilm formation both in vitro and in vivo. Interestingly, overexpression of ZCF15 impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression of ZCF15 and ZCF26 demonstrated their role in reprogramming cellular metabolism by regulating central metabolism including glyoxylate and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, including ZCF15 and ZCF26, that appear to control biofilm development through their specific role in metabolic remodeling.
PubMed: 38905306
DOI: 10.1371/journal.pbio.3002693 -
PLoS Neglected Tropical Diseases Jun 2024Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious...
BACKGROUND
Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of "prolonged fevers" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments.
METHODS
We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias.
RESULTS
196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles.
CONCLUSIONS
Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.
PubMed: 38905305
DOI: 10.1371/journal.pntd.0011978 -
PloS One 2024Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T....
Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.
Topics: Treponema pallidum; Humans; Pakistan; Syphilis; Blood Donors; Anti-Bacterial Agents; Drug Resistance, Bacterial; Male; Female; Adult; Macrolides; RNA, Ribosomal, 23S; RNA, Ribosomal, 16S; Middle Aged; Doxycycline; Young Adult
PubMed: 38905249
DOI: 10.1371/journal.pone.0305720 -
Cureus May 2024A 34-year-old male, with no history of known previous disease, employed at a ginger farm in South India, presented with a four-day history of high-grade fever and...
A 34-year-old male, with no history of known previous disease, employed at a ginger farm in South India, presented with a four-day history of high-grade fever and headache. Initially, he received symptomatic treatment but was referred due to hypotension and persistent fever. Investigations showed leucocytosis, thrombocytopenia, abnormal liver function tests, renal dysfunction, and elevated C-reactive protein. Positive results were obtained for immunoglobulin M (IgM) and scrub typhus IgM tests, indicating a coinfection, reported rarely from this region. Timely clinical suspicion, prompt laboratory diagnosis, and early treatment with doxycycline and broad-spectrum antibiotics are crucial to prevent complications and fatal outcomes in such coinfections.
PubMed: 38903293
DOI: 10.7759/cureus.60732 -
World Journal of Clinical Cases Jun 2024In addition to the non-specific symptomatology of ocular rosacea, currently, there are no reliable diagnostic tests for the disease, which may lead to its misdiagnosis....
BACKGROUND
In addition to the non-specific symptomatology of ocular rosacea, currently, there are no reliable diagnostic tests for the disease, which may lead to its misdiagnosis. Here, we report a case of ocular rosacea presenting with multiple recurrent chalazion on both eyelids.
CASE SUMMARY
A 63-year-old female patient presented with multiple chalazion and dry eyes in both eyes, with no facial erythema. Initial management done were application of steroid eye ointment on both eyelids, hot compresses, and eyelid margin cleaning; noting that there was no relief of symptoms. Surgical excision of the chalazion was done on both eyes, however, bilateral recurrence occurred post-operatively. The pathological studies showed infiltration of a small amount of fibrous tissue with many chronic inflammatory cells. Immunohistochemistry studies were positive for LL-37. Resolution of the chalazion occurred after oral administration of doxycycline and azithromycin.
CONCLUSION
Our findings show that ophthalmologists should recognize the ocular manifestations of skin diseases.
PubMed: 38898849
DOI: 10.12998/wjcc.v12.i17.3253 -
Veterinaria Italiana Mar 2024The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether...
The aim of this study was to determine the concentration of TNF-alpha (TNF-α) in dogs naturally infected with Dirofilaria immitis (D. immitis) and to assess whether there are any changes in TNF-α concentration and their dependence during therapy for heartworm disease (HWD). For this study, 14 client-owned dogs with HWD were selected. Clinical and parasitological examinations (modified Knott test for circulating microfilariae and SNAP Test IDEXX for circulating D. immitis antigen) had been used for diagnosing D. immitis and HWD. All dogs were treated with an alternative therapy for HWD (oral doxycycline 10 mg/kg b.w., once daily for 6 weeks, then alternately 4 weeks without and 2 weeks with the medication, and oral ivermectin 6-14 µg/kg b.w., every 2 weeks). The dogs blood sera at the moment of HWD diagnosis, during and at the end of therapy were frozen for further quantifying of TNF-α (Canine TNF-alpha ELISA kit, Thermo scientific). At the moment of HWD diagnosis TNF-α was detected in 9 dogs (7.21±12.44 pg/ml). Concentration of TNF-α was not significantly change during the therapy, neither related to the level of D. immitis antigen nor to antigen level changes. The alternative therapy for HWD has no influence on TNF-α concentration dynamics.
Topics: Animals; Dogs; Dirofilariasis; Dog Diseases; Tumor Necrosis Factor-alpha; Dirofilaria immitis; Male; Female; Doxycycline; Ivermectin
PubMed: 38898794
DOI: 10.12834/VetIt.2662.22847.2 -
International Journal of Pharmaceutics Jun 2024Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for...
Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC of PolyMet/PCL@DOX was 7.4 μg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.
PubMed: 38897492
DOI: 10.1016/j.ijpharm.2024.124358 -
Environmental Pollution (Barking, Essex... Jun 2024We compared the ability of one emergent (Sagittaria montevidensis), two floating (Salvinia minima and Lemna gibba), and one heterophyllous species (Myriophyllum...
We compared the ability of one emergent (Sagittaria montevidensis), two floating (Salvinia minima and Lemna gibba), and one heterophyllous species (Myriophyllum aquaticum) to simultaneously remove sulfamethoxazole, sulfadiazine, ciprofloxacin, enrofloxacin, norfloxacin, levofloxacin, oxytetracycline, tetracycline, doxycycline, azithromycin, amoxicillin, and meropenem from wastewater in a mesocosm-scale constructed wetland over 28 days. Antibiotic concentrations in plants and effluent were analyzed using an LC-MS/MS to assess the removal rates and phytoremediation capacities. M. aquaticum did not effectively mitigate contamination due to poor tolerance and survival in effluent conditions. S. minima and L. gibba demonstrated superior efficiency, reducing the antibiotic concentrations to undetectable levels within 14 days, while S. montevidensis achieved this result by day 28. Floating macrophytes emerge as the preferable choice for remediation of antibiotics compared to emergent and heterophyllous species. Antibiotics were detected in plant tissues at concentrations ranging from 0.32 to 29.32 ng g fresh weight, highlighting macrophytes' ability to uptake and accumulate these contaminants. Conversely, non-planted systems exhibited a maximum removal rate of 65%, underscoring the persistence of these molecules in natural environments, even after the entire experimental period. Additionally, macrophytes improved effluent quality regardless of species by reducing total soluble solids and phosphate concentrations and mitigating ecotoxicological effects. This study underscores the potential of using macrophytes in wastewater treatment plants to enhance overall efficiency and prevent environmental contamination by antibiotics, thereby mitigating the harmful impact on biota and antibiotic resistance. Selecting appropriate plant species is crucial for successful phytoremediation in constructed wetlands, and actual implementation is essential to validate their effectiveness and practical applicability.
PubMed: 38897277
DOI: 10.1016/j.envpol.2024.124376 -
Ocular Immunology and Inflammation Jun 2024To report a rare presentation of a proven case of infection presenting as multifocal choroiditis with recurrent choroidal neovascular membrane (CNVM) in one eye,...
PURPOSE
To report a rare presentation of a proven case of infection presenting as multifocal choroiditis with recurrent choroidal neovascular membrane (CNVM) in one eye, initially misdiagnosed as punctate inner choroidopathy and later developed serpiginous-like choroiditis in the other eye.
METHODS
Retrospective case report with a review of existing literature.
RESULTS
A 30-year-old women presented with metamorphopsia (OD) and best-corrected visual acuity (BCVA) of 6/24 (OD) and was diagnosed to have punctate inner choroidopathy with CNVM (OD). Since then, she had received four intravitreal anti-vascular endothelial growth factor injections over 3 years. Two years later, she developed a slowly progressing choroidal lesion radiating from the disc in a serpiginoid manner in the left eye. There was no vitritis. Labs revealed a positive QuantiFERON-TB Gold test. High-resolution computed tomography of the thorax showed sub-centimetre noncalcified lymph nodes in subcarinal and perivascular regions, minimal pleural thickening in left lower zone, minimal pericardial effusion, bronchiectatic changes, and fibrotic strands in right middle and left lower lobes. Bronchoalveolar lavage grew intracellularae (matrix-assisted laser desorption/ionization time-of-flight mass spectrometry). She was given a course of clarithromycin, moxifloxacin, rifampicin, and doxycycline for 12 months. Though the right eye remained stable, choroidal lesion in the left eye continued to progress threatening the fovea, requiring oral steroids, methotrexate, and an intravitreal dexamethasone implant. At the last follow-up, her BCVA was 6/18 (OD) and 6/6 (OS). Both eyes were stable.
CONCLUSION
This case highlights a rare presentation of proven infection presenting as multifocal choroiditis with recurrent CNVM in one eye and serpiginous-like choroiditis in the other eye, requiring aggressive treatment to salvage the vision.
PubMed: 38889671
DOI: 10.1080/09273948.2024.2367654