Chronic pulmonary aspergillosis (CPA) is a spectrum of several progressive disease manifestations caused by Aspergillus species in patients with underlying structural lung diseases. Duration of symptoms longer than three months distinguishes CPA from acute and subacute invasive pulmonary aspergillosis. CPA affects over 3 million individuals worldwide. Its diagnostic approach requires a thorough Clinical, Radiological, Immunological and Mycological (CRIM) assessment. The diagnosis of CPA requires (1) demonstration of one or more cavities with or without a fungal ball present or nodules on chest imaging, (2) direct evidence of Aspergillus infection or an immunological response to Aspergillus species and (3) exclusion of alternative diagnoses, although CPA and mycobacterial disease can be synchronous. Aspergillus antibody is elevated in over 90% of patients and is the cornerstone for CPA diagnosis. Long-term oral antifungal therapy improves quality of life, arrests haemoptysis and prevents disease progression. Itraconazole and voriconazole are alternative first-line agents; voriconazole is preferred for patients with contra-indications to itraconazole and in those with severe disease (including large aspergilloma). In patients co-infected with tuberculosis (TB), it is not possible to treat TB with rifampicin and concurrently administer azoles, because of profound drug interactions. In those with pan-azole resistance or intolerance or progressive disease while on oral triazoles, short-term courses of intravenous liposomal amphotericin B or micafungin is used. Surgery benefits patients with well-circumscribed simple aspergillomas and should be offered earlier in low-resource settings.
Summary Chronic pulmonary aspergillosis (CPA) is a potentially life‐threatening debilitating lung disease necessitating long‐term oral antifungal treatment. However, development of antifungal‐resistant isolates of Aspergillus and major toxicities requiring discontinuation of treatment limits their use. Intravenous (IV) antifungals are an option in this group of patients. We comprehensively evaluate the response rates to IV antifungals in the management of CPA. We searched Medline and Embase databases to select clinical studies providing information about IV amphotericin B or an echinocandin for the treatment of CPA from inception to May 2020. Reviews, single‐case reports and case series reporting <10 patients were excluded. We evaluated 12 eligible studies. A total of 380 patients received amphotericin B (n = 143) or an echinocandin (n = 237) and were included in the meta‐analysis. In a pooled analysis, overall response to IV antifungals was 61% ((95% confidence interval (CI): 52%‐70%; I2 = 73.3%; P < .001), to amphotericin B was 58% (95% CI: 36%‐80%; I2 = 86.6%; P < .001) and to echinocandins was 62% (95% CI: 53%‐72%; I2 = 63.6%; P < .001). Amphotericin B courses were usually doses at slightly <1 mg/Kg (deoxycholate) or 3 mg/Kg (liposomal) for 2‐3 weeks. Micafungin doses varied from 12.5 to 300 mg (frequently, 150 mg) daily for at least 3 weeks, and sometimes much longer. Liposomal amphotericin B was well tolerated, but led to renal function loss in 25% of patients. Adverse events were observed in 5‐35.3% of patients receiving echinocandins, none of which was considered major. Intravenous antifungals have a place in the management of CPA. A head‐to‐head comparison of amphotericin B and echinocandins is lacking, and future studies should look at evaluating short‐ and longer‐term outcomes of these agents.
Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma capsulatum, is an uncommon multisystem disease with a global distribution. The spectrum of clinical manifestations ranges from an asymptomatic or minimally symptomatic acute pulmonary disease following inhalation of a large inoculum of Histoplasma microconidia to chronic pulmonary disease in patients with underlying structural lung disease. It also extends to acute progressive disseminated disease in patients with severe immunodeficiency. Generally, antifungal therapy is indicated for patients with progressive acute pulmonary histoplasmosis, chronic pulmonary histoplasmosis and acute progressive disseminated histoplasmosis. In immunocompetent patients, acute pulmonary histoplasmosis may be a self-limiting disease without the need for systemic antifungal therapy. Oral triazole antifungal drugs alone are recommended for less severe disease. However, moderate-to-severe acute pulmonary histoplasmosis requires intravenous amphotericin B therapy for at least 1-2 weeks followed by oral itraconazole for at least 12 weeks. For acute progressive disseminated histoplasmosis, intravenous amphotericin B therapy is given for at least 2 weeks (4-6 weeks if meningeal involvement) or until a patient can tolerate oral therapy, followed by oral itraconazole (or an alternative triazole) for at least 12 months. Chronic cavitary pulmonary histoplasmosis is treated with oral itraconazole for 1-2 years. There is insufficient evidence to support the use of isavuconazole or the echinocandins for the treatment of histoplasmosis.
Introduction hepatitis B virus (HBV) is one of the commonest causes of acute and chronic liver diseases worldwide. HBV can be transmitted by exposure to infected blood and human secretions through sharp injuries and splashes. Health workers are among the most high-risk groups because they regularly interact with patients. A seroprevalence survey conducted in Uganda in 2014 found a higher prevalence of HBV in Gulu Municipality compared to the rest of Uganda. Methods a cross-sectional study was conducted among health workers in Gulu Regional Hospital. A stratified random sampling was used. Knowledge ratings and Likert scale were used to score knowledge, attitudes and risks of HBV infections in a qualitative assessment. Ethical approval was obtained and SPSS was used for data analysis. A p-value less than 0.05 was considered significant. Results one hundred and twenty-six (126) respondents participated; 65 (51.6%) were male, 80 (63.5%) were aged 20-29 years, 74 (58.7%) were not married, 86 (68.3%) had a work experience of 0-9 years, 64 (50.8%) had good knowledge, 90(71.4%) had positive attitude, 114 (90.5%) had high to very high pre-exposure risks, and 75 (59.5%) had moderate to high exposure and post-exposure risks. There was no significant difference in knowledge ( X 2 = 13.895; p = 0.178) and work experience ( X 2 = 21.196; p = 0.097) among the health workers. Conclusion there is a high pre-exposure, exposure and post-exposure risks of HBV infection among health workers in Gulu Hospital. There is need to augment awareness on HBV infection and design strategies to strengthen and implement infection control measures including HBV vaccination among health workers.
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