RESUMO
Tuberculosis (TB) is the top bacterial infectious disease killer and one of the top ten causes of death worldwide. The emergence of strains of multiple drug-resistant tuberculosis (MDR-TB) has pushed our available stock of anti-TB agents to the limit of effectiveness. This has increased the urgent need to develop novel treatment strategies using currently available resources. An adjunctive, host-directed therapy (HDT) designed to act on the host, instead of the bacteria, by boosting the host immune response through activation of intracellular pathways could be the answer. The integration of multidisciplinary approaches of repurposing currently FDA-approved drugs, with a targeted drug-delivery platform is a very promising option to reduce the long timeline associated with the approval of new drugs - time that cannot be afforded given the current levels of morbidity and mortality associated with TB infection. The deficiency of vitamin A has been reported to be highly associated with the increased susceptibility of TB. All trans retinoic acid (ATRA), the active metabolite of vitamin A, has proven to be very efficacious against TB both in vitro and in vivo. In this review, we discuss and summarise the importance of vitamin A metabolites in the fight against TB and what is known regarding the molecular mechanisms of ATRA as a host-directed therapy for TB including its effect on macrophages cytokine profile and cellular pathways. Furthermore, we focus on the issues behind why previous clinical trials with vitamin A supplementation have failed, and how these issues might be overcome.
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We aimed to benchmark the quality of care and describe characteristics of patients newly attending the HIV clinic at differing time points over the past 10 years, against the Infectious Disease Society of America HIV/AIDS performance measures. We performed a retrospective analysis of records for patients newly attending the HIV clinic in 2011, 2016 and 2018. There was an increase in male attendees in 2018 and 2016 compared to 2011 (88%, 88% vs. 59% p < .001), viral suppression rates were 97%, 83% and 99% (p < .001), respectively. We observed an increase in patients of South American origin over time. Acquisition risk changed, with increased proportion of MSM (24% in 2011 vs 78% in 2018, p < .001), lower rates of heterosexual (20% in 2018 vs 48% in 2011, p < .001) and IDU transmission (1.5% in 2018 vs 24% in 2011, p < .001). There were lower rates of Chlamydia trachomatis and Neisseria gonorrhoeae testing in 2018 (72%, p < .001), compared to 2016 (84%) and 2011 (83%). Hepatitis B virus vaccination and pneumococcal vaccine rates are declining (p < .001). We demonstrate the changes in both ethnicity and risk of acquisition over time, high rates of antiretroviral therapy prescription and viral suppression, and highlight the importance of health prevention with sexual health screening and vaccination in this population.
Assuntos
Infecções por Chlamydia , Gonorreia , Infecções por HIV , Minorias Sexuais e de Gênero , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Demografia , Gonorreia/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: The first pillar of the End-TB Strategy is "early diagnosis and prompt treatment". Nevertheless, long delays in starting tuberculosis (TB) treatment are reported. We aimed to describe the demographics and clinical features of TB in the west of Ireland and better understand the delays in treatment. METHODS: We conducted a retrospective chart review of all patients diagnosed with active TB who attended the Galway University Hospital (GUH) TB clinic from 2014 to 2018. RESULTS: Eighty-five patients were diagnosed with TB and attended our clinic. Ten (12%) patients were receiving immunosuppressive therapy, 8 (9%) had drug resistance, and 41 (48%) had extra-pulmonary disease. Patients with extra-pulmonary disease had a longer length of stay before treatment (11 vs. 4 days; p = 0.006). Patients older than 55 had a longer length of stay before (16 vs. 5 days, p = 0.0001) and during (36 vs. 11 days, p = 0.004) treatment and were readmitted more frequently than younger patients. A total of 36% of patients were born outside Ireland. Non-Irish patients were younger (mean age 35 vs 48; p = 0.004) and more frequently had drug resistance (19% vs. 4%, p = 0.02). The median time from symptom onset to hospital presentation was 76 days (IQR 35-146 days) and the median time from first hospital presentation to TB treatment was 11 days (IQR 5-51 days). CONCLUSION: TB patients experienced long symptom durations in the community prior to presentation. Many TB patients experienced delays in diagnosis and treatment following presentation. Both pre-hospital and in-hospital delays need to be addressed in order to 'End-TB'.
Assuntos
Tuberculose Pulmonar , Tuberculose , Adulto , Estudos Transversais , Diagnóstico Tardio , Humanos , Irlanda/epidemiologia , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológicoRESUMO
Cystic echinococcosis (CE) is caused by the cestodes of the Echinococcus granulosus sensu lato complex and, in the majority of cases, is associated with hepatic or pulmonary involvement. Human CE is not thought to be endemic in Ireland. We describe the first reported case of human CE possibly acquired in Ireland.
Assuntos
Equinococose/diagnóstico , Echinococcus granulosus/fisiologia , Idoso de 80 Anos ou mais , Animais , Antiplatelmínticos/administração & dosagem , Colangite , Equinococose/diagnóstico por imagem , Equinococose/tratamento farmacológico , Evolução Fatal , Feminino , Humanos , IrlandaRESUMO
BACKGROUND: High-cost, high-need users are defined as patients who accumulate large numbers of emergency department visits and hospital admissions that might have been prevented by relatively inexpensive early interventions and primary care. This phenomenon has not been previously described in HIV-infected individuals. METHODS: We analyzed the health records of HIV-infected individuals using scheduled or unscheduled inpatient or outpatient health care in St James's Hospital, Dublin, Ireland, from October 2014 to October 2015. RESULTS: Twenty-two of 2063 HIV-infected individuals had a cumulative length of stay >30 days in the study period. These individuals accrued 99 emergency department attendances and 1581 inpatient bed days, with a direct cost to the hospital of >1 million during the study period. Eighteen of 22 had potentially preventable requirements for unscheduled care. Two of 18 had a late diagnosis of HIV. Sixteen of 18 had not been successfully engaged in outpatient HIV care and presented with consequences of advanced HIV. Fourteen of 16 of those who were not successfully engaged in care had ≥1 barrier to care (addiction, psychiatric disease, and/or homelessness). CONCLUSIONS: A small number of HIV-infected individuals account for a high volume of acute unscheduled care. Intensive engagement in outpatient care may prevent some of this usage and ensuing costs.
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BACKGROUND: We initiated an emergency department (ED) opt-out screening programme for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) at our hospital in Dublin, Ireland. The objective of this study was to determine screening acceptance, yield and the impact on follow-up care. METHODS: From July 2015 through June 2018, ED patients who underwent phlebotomy and could consent to testing were tested for HIV, HBV and HCV using an opt-out approach. We examined acceptance of screening, linkage to care, treatment and viral suppression using screening programme data and electronic health records. The duration of follow-up ranged from 1 to 36 months. RESULTS: Over the 36-month study period, there were 140 550 ED patient visits, of whom 88 854 (63.2%, 95% CI 63.0% to 63.5%) underwent phlebotomy and 54 817 (61.7%, 95% CI 61.4% to 62.0%) accepted screening for HIV, HBV and HCV, representing 41 535 individual patients. 2202 of these patients had a positive test result. Of these, 267 (12.1%, 95% CI 10.8% to 13.6%) were newly diagnosed with an infection and 1762 (80.0%, 95% CI 78.3% to 81.7%) had known diagnoses. There were 38 new HIV, 47 new HBV and 182 new HCV diagnoses. 81.5% (95% CI 74.9% to 87.0%) of known patients who were not linked were relinked to care after screening. Of the new diagnoses, 86.2% (95% CI 80.4 to 90.8%) were linked to care. CONCLUSION: Although high proportions of patients had known diagnoses, our programme was able to identify many new infected patients and link them to care, as well as relink patients with known diagnoses who had been lost to follow-up.
Assuntos
Comportamento de Escolha , Serviços de Diagnóstico/estatística & dados numéricos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Programas de Rastreamento/normas , Adulto , Serviço Hospitalar de Emergência/organização & administração , Feminino , Infecções por HIV/diagnóstico , Hepatite B/diagnóstico , Hepatite C/diagnóstico , Humanos , Irlanda , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-IdadeRESUMO
A 65-year-old male patient presented with fever, fast atrial fibrillation and frank haematuria on return to Ireland from travel in East Africa. He had a systolic murmur leading to a clinical suspicion of endocarditis. He had no specific clinical features of diphtheria. Blood cultures were taken and empiric therapy commenced with benzylpenicillin, vancomycin and gentamicin. Corynebacterium diphtheriae was detected on blood culture. The isolate was submitted to a reference laboratory for evaluation of toxigenicity. While initially there was concern regarding the possibility of myocarditis, a clinical decision was made not to administer diphtheria antitoxin in the absence of clinical features of respiratory diphtheria, in the presence of invasive infection and with presumptive previous immunisation. There is no specific guidance on the role of antitoxin in this setting. The issue is not generally addressed in previous reports of C. diphtheriae blood stream infection.