Evaluation and comparison of automated and manual ELISA for diagnosis of chronic pulmonary aspergillosis (CPA) in Indonesia

Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.

Chronic pulmonary aspergillosis (CPA) is an uncommon and problematic pulmonary disease, complicating many other respiratory disorders, thought to affect ~240 000 people in Europe. The most common form of CPA is chronic cavitary pulmonary aspergillosis (CCPA), which untreated may progress to chronic fibrosing pulmonary aspergillosis. Less common manifestations include: Aspergillus nodule and single aspergilloma. All these entities are found in non-immunocompromised patients with prior or current lung disease. Subacute invasive pulmonary aspergillosis (formerly called chronic necrotising pulmonary aspergillosis) is a more rapidly progressive infection (<3 months) usually found in moderately immunocompromised patients, which should be managed as invasive aspergillosis. Few clinical guidelines have been previously proposed for either diagnosis or management of CPA. A group of experts convened to develop clinical, radiological and microbiological guidelines. The diagnosis of CPA requires a combination of characteristics: one or more cavities with or without a fungal ball present or nodules on thoracic imaging, direct evidence of Aspergillus infection (microscopy or culture from biopsy) or an immunological response to Aspergillus spp. and exclusion of alternative diagnoses, all present for at least 3 months. Aspergillus antibody (precipitins) is elevated in over 90% of patients. Surgical excision of simple aspergilloma is recommended, if technically possible, and preferably via video-assisted thoracic surgery technique. Long-term oral antifungal therapy is recommended for CCPA to improve overall health status and respiratory symptoms, arrest haemoptysis and prevent progression. Careful monitoring of azole serum concentrations, drug interactions and possible toxicities is recommended. Haemoptysis may be controlled with tranexamic acid and bronchial artery embolisation, rarely surgical resection, and may be a sign of therapeutic failure and/or antifungal resistance. Patients with single Aspergillus nodules only need antifungal therapy if not fully resected, but if multiple they may benefit from antifungal treatment, and require careful follow-up.

To estimate the global burden of chronic pulmonary aspergillosis (CPA) after pulmonary tuberculosis (PTB), specifically in cases with pulmonary cavitation. PTB rates were obtained from the World Health Organization and a scoping review of the literature was conducted to identify studies on residual pulmonary cavitation after PTB and estimate the global incidence of CPA after PTB. Having established that from 21% (United States of America) to 35% (Taiwan, China) of PTB patients developed pulmonary cavities and that about 22% of these patients developed CPA, the authors applied annual attrition rates of 10%, 15% and 25% to estimate the period prevalence range for CPA over five years. Analysis was based on a deterministic model. In 2007, 7.7 million cases of PTB occurred globally, and of them, an estimated 372,000 developed CPA: from 11,400 in Europe to 145,372 in South-East Asia. The global five-year period prevalence was 1,174,000, 852,000 and 1,372,000 cases at 15%, 25% and 10% annual attrition rates, respectively. The prevalence rate ranged from < 1 case per 100,000 population in large western European countries and the United States of America to 42.9 per 100,000 in both the Democratic Republic of the Congo and Nigeria. China and India had intermediate five-year period prevalence rates of 16.2 and 23.1 per 100,000, respectively. The global burden of CPA as a sequel to PTB is substantial and warrants further investigation. CPA could account for some cases of smear-negative PTB. Since CPA responds to long-term antifungal therapy, improved case detection should be urgently undertaken.