RESUMO
Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including the infection with human immunodeficiency virus (HIV). Single nucleotide polymorphisms (SNPs) in TLRs such as TLR4 1063A/G and 1363C/T have been found to be associated with changes in CD4 count, viral load (VL), and disease progression during HIV infection. However, the association of these SNPs with the pathogenesis during HIV infection is controversial. We investigated the frequency of TLR4 1063A/G and 1363C/T SNPs in 168 Omani donors [68 HIV-infected patients (>3% of Omani HIV-infected patients) and 100 healthy controls] and the association of these SNPs with the VL, CD8 and CD4 counts, and the immune recovery after cART as observed by CD4 T cell increase. SNPs were analyzed after the amplification of the regions that contain them by polymerase chain reaction (PCR) and sequencing of the PCR products. The TLR4 1063GG genotype was detected in the HIV-infected group only. No association was found between the studied SNPs and the average VL during 1 year of infection, the average CD4 and CD8 count during 1 year of viremia, the nadir CD4 count, the CD4 count when the patient reached VL < 50 copies/mL due to cART, and the ratio of the CD4 count 3 and 6 months after reaching VL < 50 copies/mL after cART to the last CD4 count before reaching VL < 50 copies/mL. Our study suggests that TLR4 (1063A/G and 1363C/T) SNPs have no association with the VL or the CD4 and CD8 counts during HIV infection.
Assuntos
Infecções por HIV/genética , Polimorfismo de Nucleotídeo Único , Receptor 4 Toll-Like/genética , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Estudos de Casos e Controles , Feminino , Infecções por HIV/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Omã , Carga ViralRESUMO
C-C motif chemokine receptor-5 (CCR5) is a pro-inflammatory receptor that binds to chemokines and facilitates the entry of the R5 strain of HIV-1. A number of polymorphisms were identified within the promoter and coding regions of the CCR5 gene, some of which have been found to affect the protein expression and thus receptor function. Although several CCR5 polymorphisms were shown to vary widely in their distribution among different ethnic populations, there has been no study addressing the potential variants of the CCR5 gene in the Omani population. The aim of this study was to identify the polymorphic sites that exist within the CCR5 gene in Omanis. Blood samples were collected from 89 Omani adult individuals, and genomic DNA was amplified by polymerase chain reaction and sequenced to identify the polymorphic sites. The distribution of the detected variants was examined and compared with the previously published data. Four new indels were detected of 32 variable positions, -2973A/-, -2894A/-, -2827TA/- and -2769T/-, and all were located in the 5'UTR. Furthermore, two new mutations, -2248G/A and +658A/G, were observed for the first time; the -2248G/A was detected in the intron 1 region in one subject and +658A/G in the coding region of the CCR5 in another subject. In silico analysis showed that the novel variations in the 5'UTR may have effects on the transcription factor binding sites. Therefore, this study demonstrates the presence of two new SNPs and four novel indels in the CCR5 gene in the Omani population. Our findings support the wide spectrum of genetic diversity reported within the CCR5 gene region among different ethnic groups.
Assuntos
Polimorfismo Genético , Receptores CCR5/genética , Regiões 5' não Traduzidas , Adulto , Alelos , Sítios de Ligação , Biologia Computacional/métodos , Frequência do Gene , Predisposição Genética para Doença , Infecções por HIV/genética , Haplótipos , Humanos , Mutação INDEL , Desequilíbrio de Ligação , Mutação , Omã , Mapeamento Físico do Cromossomo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Receptores CCR2/genética , Fatores de Transcrição/metabolismoRESUMO
Routine HIV testing of all pregnant women in Oman has been introduced without prior knowledge of women's attitudes towards testing or their behaviour in the event of a positive test. This study recruited 1000 Omani pregnant women from antenatal clinics to explore their knowledge of HIV/AIDS, attitudes towards HIV testing and intended behaviours in the event of a positive test. Mother-to-child transmission was recognized by 86.6% of the women but only 21.0% knew that it was preventable and a few acknowledged the important role of antiviral drugs. Half of the women (51.9%) reported having been tested for HIV and 75.8% agreed about routine HIV testing for all pregnant women. A higher level of knowledge was significantly associated with a favourable intended behaviour related to voluntary testing, disclosure and seeking professional assistance in the event of a positive HIV test. The results are discussed in relation to opt-in and opt-out approaches to voluntary testing during pregnancy.
Assuntos
Sorodiagnóstico da AIDS/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/prevenção & controle , Gestantes/psicologia , Cuidado Pré-Natal/normas , Sorodiagnóstico da AIDS/normas , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/transmissão , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Omã , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Cuidado Pré-Natal/métodos , Adulto JovemRESUMO
Background: Bloodstream infections caused by carbapenem-resistant Gram-negative bacteria represent a major therapeutic challenge to clinicians worldwide. This study examined the epidemiology of carbapenem and colistin resistance in Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii blood isolates in an academic institution in Oman. Methods: Adult patients with bloodstream infections caused by Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii, between January 1, 2017, and December 31, 2020, were identified. Rates of carbapenem resistance, carbapenem-colistin dual resistance, and 30-day all-cause mortality were examined. Results: 585 non-repeat bloodstream infections due to Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii were identified during the study period. OXA-48 was the most prevalent carbapenemase gene in carbapenem-resistant K. pneumoniae blood isolates. Carbapenem resistance was observed in 160 (27.7%) of blood isolates, with 131 (81.9%) of these being healthcare-onset cases. Carbapenem resistance was highest in Acinetobacter baumannii (80.4%), followed by Klebsiella pneumoniae (46.4%), and Pseudomonas aeruginosa (29.9%). Sixteen (13.4%) of the carbapenem-resistant blood isolates were found to be colistin resistant. Thirty-day all-cause mortality was 68.1% in patients with bloodstream infections caused by carbapenem-resistant isolates, versus 21.3% in patients with bloodstream infections caused by carbapenem-susceptible isolates. Conclusion: The prevalence of carbapenem resistance and carbapenem-colistin dual resistance in Gram-negative blood culture isolates from patients with bloodstream infections is unacceptably high. Patients with bloodstream infections due to carbapenem-resistant isolates had substantially higher mortality.
RESUMO
OBJECTIVE: The aim of this study was to evaluate the efficacy of anakinra in patients who were admitted to hospital for severe COVID-19 pneumonia requiring oxygen therapy. METHODS: A prospective, open-label, interventional study in adults hospitalized with severe COVID-19 pneumonia was conducted. Patients in the interventional arm received subcutaneous anakinra (100 mg twice daily for 3 days, followed by 100 mg daily for 7 days) in addition to standard treatment. Main outcomes were the need for mechanical ventilation and in-hospital death. Secondary outcomes included successful weaning from supplemental oxygen and change in inflammatory biomarkers. Outcomes were compared with those of historical controls who had received standard treatment and supportive care. RESULTS: A total of 69 patients were included: 45 treated with anakinra and 24 historical controls. A need for mechanical ventilation occurred in 14 (31%) of the anakinra-treated group and 18 (75%) of the historical cohort (p < 0.001). In-hospital death occurred in 13 (29%) of the anakinra-treated group and 11 (46%) of the historical cohort (p = 0.082). Successful weaning from supplemental oxygen to ambient air was attained in 25 (63%) of the anakinra-treated group compared with 6 (27%) of the historical cohort (p = 0.008). Patients who received anakinra showed a significant reduction in inflammatory biomarkers. CONCLUSION: In patients with severe COVID-19 pneumonia and high oxygen requirement, anakinra could represent an effective treatment option and may confer clinical benefit. TRIAL REGISTRATION NUMBER: ISRCTN74727214.
Assuntos
COVID-19/terapia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Oxigênio/uso terapêutico , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração ArtificialRESUMO
Herpes simplex virus is the most common cause of severe and potentially fatal sporadic encephalitis worldwide. Recurrence of neurologic symptoms after resolution of the initial episode of HSV encephalitis and despite adequate treatment with intravenous acyclovir is well recognized albeit rare. Most of these recurrences had no evidence of replicating virus and are immune in nature with only a minority of these recurrences representing true virologic relapses. Immunocompromised patients are predominantly at greater risk for virologic relapse of HSV encephalitis with potentially severe and at times fatal consequences. We describe a patient with small cell lung cancer and brain metastasis who underwent chemotherapy, treatment with dexamethasone and whole brain radiotherapy who subsequently suffered two episodes of HSV encephalitis three months and seven months after completion of radiotherapy and while on dexamethasone treatment.
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Erysipelothrix rhusiopathiae (E. rhusiopathiae) is a rare occupational opportunistic Gram-positive bacillus. Infections caused by E. rhusiopathiae are principally a sequel of occupational and recreational exposures to infected animals. Infective endocarditis is a classic, albeit it infrequent, manifestation of invasive infection with this bacterium. We present a case of E. rhusiopathiae mitral valve endocarditis in a farmer with psoriasis presented with acute intractable heart failure requiring valve replacement surgery. E. rhusiopathiae was identified by 16S rRNA-based gene sequencing from culture-negative, surgically excised mitral valve leaflets.
RESUMO
The case of a patient with disseminated strongyloidiasis following chemotherapy for lymphoplasmacytic lymphoma is presented.
Assuntos
Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Hemorragia/tratamento farmacológico , Ivermectina/administração & dosagem , Meningite/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Estrongiloidíase/complicações , Animais , Hemorragia/etiologia , Humanos , Masculino , Meningite/etiologia , Pessoa de Meia-Idade , Choque Séptico/etiologia , Strongyloides stercoralis/fisiologia , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologiaRESUMO
Basidiobolomycosis is rare infection caused by the saprophytic fungus Basidiobolus ranarum. Gastrointestinal basidiobolomycosis is an infrequent, albeit, increasingly reported, emerging form of the disease and typically affects immunocompetent individuals with potentially grave sequelae if unrecognized. Acquaintance with this exceptionally rare fungus and its potential for presenting as gastrointestinal mass masquerading as colonic malignancy is critical for timely diagnosis, appropriate treatment and successful clinical outcome. We report a case of gastrointestinal basidiobolomycosis masquerading as colonic malignancy in a 29-year-old Omani patient successfully treated with combination of surgery and prolonged azole antifungal therapy.
RESUMO
BACKGROUND: Bacteraemia due to carbapenem-resistant gram-negative bacteria is challenging. This study examined the burden of carbapenem and colistin resistance in Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii bacteraemia in Oman. METHODS: Adult patients admitted to Sultan Qaboos University Hospital between January 1, 2007 and December 31, 2016 with positive blood cultures for P. aeruginosa, A. baumannii, or K. pneumoniae were identified. Rates of carbapenem resistance, trends in prevalence, and 30-day all-cause mortality were examined. RESULTS: Two hundred and twenty-seven (29.8%) of 761 bacteraemia cases due to these three isolates were carbapenem-resistant, with 87.2% being healthcare-associated. A. baumannii caused 52% of all carbapenem-resistant bacteraemia, K. pneumoniae caused 30%, and P. aeruginosa caused 18%. Rates of carbapenem resistance in P. aeruginosa, A. baumannii, and K. pneumoniae bacteraemia increased from 20%, 67%, and 0%, respectively, in 2007 to 25%, 86%, and 35%, respectively, in 2016. Seventeen (7.9%) carbapenem-resistant bacteraemia cases were also colistin-resistant. Thirty-day all-cause mortality was 62% in patients with carbapenem-resistant bacteraemia and 22% in patients with carbapenem-sensitive bacteraemia. CONCLUSIONS: The prevalence of carbapenem-resistant K. pneumoniae, A. baumannii, and P. aeruginosa bacteraemia is increasing alarmingly in Oman, with a large proportion of K. pneumoniae and P. aeruginosa demonstrating additional resistance to colistin. Patients with carbapenem-resistant bacteraemia had higher 30-day all-cause mortality.
Assuntos
Acinetobacter baumannii/isolamento & purificação , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Carbapenêmicos/uso terapêutico , Colistina/uso terapêutico , Farmacorresistência Bacteriana , Klebsiella pneumoniae/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/fisiologia , Adulto , Bacteriemia/tratamento farmacológico , Feminino , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Omã , Prevalência , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/fisiologiaRESUMO
BACKGROUND: Toll-like receptors (TLRs) are essential elements of the innate immune response to different infections including HIV-1 infection. The single-nucleotide polymorphisms (SNPs) in TLRs have been associated with CD4T cell count and HIV disease progression. The TLR7 (Gln11Leu) SNP was shown to be associated with a rapid decline of CD4T cell count. A relation between TLR9 (1635A/G) SNP and CD4T cells count in HIV-infected patients is suggested, although the outcome associated with this SNP is still controversial. OBJECTIVES: To determine the relation of the TLR7 (Gln11Leu) and TLR9 (1635A/G) SNPs with the damage to the immune system during HIV infection as reflected by the average CD4T cell count. METHODS: A total of 63 HIV-infected patients and 100 healthy individuals (controls) were enrolled in this study. The above named SNPs were analyzed after amplification of the regions that potentially contain the SNPs by polymerase chain reaction (PCR) and sequencing of the PCR products. The frequency of these SNPs and their relation with the CD4T cell count were investigated. RESULTS: The TLR7 (AA) genotype 'Gln' had a trend toward being associated with a CD4T cell count >400cells/µl after controlling viremia via HAART. Additionally, the TLR9 1635 (GG) genotype was associated with a low average CD4T cell count and the TLR9 1635 (AG) genotype was significantly related to a higher average CD4T cell count during the viremic period in HIV-infected patients. CONCLUSION: The results of this longitudinal study supports the presence of an association between the TLR9 (1635A/G) genotype and the CD4T cell count, which helps clarifying the controversial results regarding this association. It also suggests that the CD4T cell count during the viremic period might be linked to the combination of both TLR7 (Gln11Leu) and TLR9 (1635A/G) genotypes. These results may help predicting the damage to the immune system, and thus impacting the planning for novel anti-HIV strategies.
Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1/imunologia , Polimorfismo de Nucleotídeo Único , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/genética , Adulto , Alelos , Substituição de Aminoácidos , Terapia Antirretroviral de Alta Atividade , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
OBJECTIVES: The aim of this study was to describe the antimicrobial prescription patterns of patients with hematological malignancies who developed febrile neutropenia (FN) at Sultan Qaboos University Hospital (SQUH) in Oman. METHODS: This was a retrospective observational study covering a period of 3 years (January 2007-February 2010). FN episodes were studied in patients with hematological malignancies in three different wards at SQUH. RESULTS: A total of 176 FN episodes were analyzed. Overall, 64% of the 107 patients studied experienced at least 2 episodes during the analysis period. Approximately, 69% of the febrile neutropenia episodes had severe neutropenia. The duration of neutropenia was less than 1 week in the majority of the episodes (57%). The mean duration of treatment was approximately 7 days, with no significant difference between specialties or different types of malignancies. Only 34 (19%) episodes had positive cultures, and most of these were from blood samples (30 episodes, 88%). The majority of isolates were gram-negative organisms (63%). The initial empirical treatment included monotherapy (37%), dual therapy (60%) and triple therapy (3%). CONCLUSIONS: This study demonstrates that there is a large variation in the antimicrobial treatment of FN episodes in patients with hematological malignancies at SQUH. All chosen drugs were within international guideline recommendations.