Publications by authors named "Daniela E Kirwan"

Article Synopsis
  • * Researchers evaluated 140 participants using both traditional methods (qPCR and cryptococcal antigen tests) and advanced techniques (metagenomic next-generation sequencing) to identify infections like cerebral toxoplasmosis and cryptococcal meningitis.
  • * Results showed that only 34% were diagnosed with an infection using any method, indicating the need for improved diagnostic tests to better detect central nervous system infections in this vulnerable population.
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Article Synopsis
  • Mycobacterium tuberculosis infection leads to significant lung damage due to inflammation in an acidic environment, but the effects of this acidity on immune response were previously unknown.
  • Research using RNA-seq revealed that acidosis alters the expression of nearly 4000 genes in infected human macrophages, particularly enhancing pathways for degrading extracellular matrix, which contributes to lung damage in Tuberculosis.
  • The study found that acidosis suppresses key cytokines involved in fighting the infection, with specific receptors related to acidosis signaling identified in both mice and TB patients, suggesting these receptors could be targeted for new therapies.
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Accurate and rapid point-of-care (PoC) diagnostics are critical to the control of the COVID-19 pandemic. The current standard for accurate diagnosis of SARS-CoV-2 is laboratory-based reverse transcription polymerase chain reaction (RT-PCR) assays. Here, a preliminary prospective performance evaluation of the QuantuMDx Q-POC SARS-CoV-2 RT-PCR assay is reported.

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Neurocysticercosis (NCC) is the most common parasitic disease affecting the nervous system and is a leading cause of acquired epilepsy worldwide, as well as cognitive impairment, especially affecting memory. The aim of this study was to evaluate the effect of NCC on spatial working memory and its correlation with hippocampal neuronal density, in a rat model of NCC. This experimental study was conducted on female ( = 60) and male ( = 73) Holtzman rats.

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Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is one of the 10 leading causes of death worldwide, especially in low-income areas. A rapid, low-cost diagnostic assay for TB with high sensitivity and specificity is not currently available. Bio-functionalized magnetic nanoparticles (MNPs) which are able to efficiently detect and concentrate biomolecules from complex biological samples, allows improving the diagnostic immunoassays.

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Severe acute respiratory coronavirus 2 (SARS-CoV-2) has spread globally since its emergence in 2019. Most SARS-CoV-2 infections generate immune responses leading to rising levels of immunoglobulins (Ig) M, A and G which can be detected using diagnostic tests including enzyme-linked immunosorbent assays (ELISA). Whilst implying previous SARS-CoV-2 infection, the detection of Ig by ELISA does not guarantee the presence of neutralising antibodies (NAb) that can prevent the virus infecting cells.

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Background: Individuals infected with SARS-CoV-2 develop neutralising antibodies. We investigated the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how this proportion varies with selected covariates.

Methodology/principal Findings: This systematic review and meta-analysis examined the proportion of individuals with SARS-CoV-2 neutralising antibodies after infection and how these proportions vary with selected covariates.

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In 2019 10 million people developed symptomatic tuberculosis (TB) disease and 1.2 million died. In active TB the inflammatory response causes tissue destruction, which leads to both acute morbidity and mortality.

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Article Synopsis
  • - The study analyzed antibody responses (IgG) in 177 individuals with SARS-CoV-2 infection in London from March to May 2020, linking antibody levels to patient demographics and outcomes.
  • - Findings revealed that 2.0%-8.5% of participants did not develop antibodies after 3-6 weeks, and those who did were generally older, had more health issues, and higher inflammatory markers.
  • - Additionally, non-White participants had stronger antibody responses that persisted over time, suggesting that serologic assays could help monitor immune responses and inform public health strategies.
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Background: Rifampicin (RIF) resistance in Mycobacterium tuberculosis is frequently caused by mutations in the rpoB gene. These mutations are associated with a fitness cost, which can be overcome by compensatory mutations in other genes, among which rpoC may be the most important. We analyzed 469 Peruvian M.

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Pyrazinamide (PZA) is an antibiotic used in first- and second-line tuberculosis treatment regimens. Approximately 50% of multidrug-resistant tuberculosis and over 90% of extensively drug-resistant tuberculosis strains are also PZA resistant. Despite the key role played by PZA, its mechanisms of action are not yet fully understood.

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Pyrazinamide (PZA) is considered the pivot drug in all tuberculosis treatment regimens due to its particular action on the persistent forms of However, no drug susceptibility test (DST) is considered sufficiently reliable for routine application. Although molecular tests are endorsed, their application is limited to known PZA resistance associated mutations. Microbiological DSTs for PZA have been restricted by technical limitations, especially the necessity for an acidic pH.

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nicotinamidase-pyrazinamidase (PZAse) is a metalloenzyme that catalyzes conversion of nicotinamide-pyrazinamide to nicotinic acid-pyrazinoic acid. This study investigated whether a metallochaperone is required for optimal PZAse activity. and PZAses (PZAse-MT and PZAse-EC, respectively) were inactivated by metal depletion (giving PZAse-MT-Apo and PZAse-EC-Apo).

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The prevalence of non-communicable diseases is increasing worldwide, which coincides with the persistence of infectious diseases including tuberculosis. These can synergistically affect individual and population health. Three non-communicable diseases that are relevant because of their associated morbidity, mortality and disability are type 2 diabetes mellitus, chronic kidney disease and rheumatoid arthritis.

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Although pyrazinamide (PZA) is a key component of first- and second-line tuberculosis treatment regimens, there is no gold standard to determine PZA resistance. Approximately 50% of multidrug-resistant tuberculosis (MDR-TB) and over 90% of extensively drug-resistant tuberculosis (XDR-TB) strains are also PZA resistant. sequencing is the endorsed test to evaluate PZA susceptibility.

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Background: The changes in body composition markers (weight, fat mass, lean mass, and BMI) over time can be associated with TB treatment outcome among HIV-infected patients. The aim of this study was to investigate whether changes in fat mass and lean mass were associated with the treatment response among patients with HIV infection and pulmonary tuberculosis.

Materials And Methods: This was a prospective cohort study.

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Rationale: Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection.

Objectives: To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB.

Methods: Markers of platelet activation were examined in plasma from 50 patients with TB before treatment and 50 control subjects.

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An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.

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The differential diagnosis for lymphadenopathy is wide and clinical presentations overlap, making obtaining an accurate diagnosis challenging. We sought to characterize the clinical and radiological characteristics, histological findings, and diagnoses for a cohort of patients with lymphadenopathy of unknown etiology. 121 Peruvian adults with lymphadenopathy underwent lymph node biopsy for microbiological and histopathological evaluation.

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Background: Cough is the major determinant of tuberculosis transmission. Despite this, there is a paucity of information regarding characteristics of cough frequency throughout the day and in response to tuberculosis therapy. Here we evaluate the circadian cycle of cough, cough frequency risk factors, and the impact of appropriate treatment on cough and bacillary load.

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Article Synopsis
  • Infection control is essential in hospitals treating HIV-positive patients to manage the heightened risk of tuberculosis (TB) they face.
  • A study in Lima, Peru, on 794 TB patient isolates revealed increasing PZA resistance linked to specific mutations in the pncA gene, particularly among those in a specialized HIV/TB ward.
  • Implementing infection control measures led to significant reductions in TB cases and multidrug-resistant strains, highlighting the importance of monitoring genetic mutations and drug resistance in controlling nosocomial TB outbreaks.
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