Histoplasmosis caused by the fungus Histoplasma capsulatum is often lethal in patients with AIDS. Urine antigen testing is highly sensitive and much quicker for diagnosis than culture. Histoplasmosis has a patchy and incompletely appreciated distribution around the world especially in South East Asia. We conducted a systematic literature review of cases of all disease forms of histoplasmosis in SE Asia, not including the Indian sub-continent. We also reviewed all histoplasmin skin test mapping studies to determine localities of exposure. We found a total of 407 cases contracted or likely to have been contracted in SE Asia. Numbers of cases by country varied: Thailand (233), Malaysia (76), Indonesia (48) and Singapore (21), with few or no cases reported in other countries. Most cases (255 (63%)) were disseminated histoplasmosis and 177 (43%) cases were HIV associated. Areas of high histoplasmin skin test sensitivity prevalence were found in Myanmar, the Philippines, Indonesia, Thailand and Vietnam - 86.4%, 26.0%, 63.6%, 36.0% and 33.7%, respectively. We have drawn maps of these data. Further study is required to ascertain the extent of histoplasmosis within SE Asia. Diagnostic capability for patients with HIV infection is urgently required in SE Asia, to reduce mortality and mis-diagnosis as tuberculosis.

Chronic pulmonary histoplasmosis (CPH) is an uncommon manifestation of Histoplasma infection with features similar to pulmonary tuberculosis (TB). In endemic areas, it may be misdiagnosed as smear-negative pulmonary TB. Historical case series mainly from patients with presumed TB described a high frequency of cavitation and poor prognosis, likely resulting from delayed presentation. More recent reports suggest that CPH can present with nodules, lymphadenopathy, or infiltrates, with cavities being a less common feature. Emphysema is the main risk factor for cavitary CPH. CPH is therefore an umbrella term, with chronic cavitary pulmonary histoplasmosis and Histoplasma nodules being the main long-term manifestations in nonimmunocompromised individuals. Diagnosis relies on a high index of suspicion, use of fungal culture of respiratory samples, antibody testing, and compatible radiological picture. Treatment with itraconazole for at least 12 months is recommended. Morbidity from CPH results from slow progression of cavities and gradual loss of lung function, especially if not recognized and treated. Studies on the epidemiology of CPH are needed in order to improve understanding of the disease.

Introduction Fungal disease has historically presented a diagnostic challenge due to its often non-specific clinical presentations, relative infrequency and reliance on insensitive and time-intensive fungal culture. Sources of data We present the recent developments in fungal diagnostics in the fields of serological and molecular diagnosis for the most clinically relevant pathogens; developments that have the potential to revolutionize fungal diagnosis through improvements in speed, simplicity and sensitivity. We have drawn on a body of evidence including recent studies and reviews demonstrating the effectiveness of antigen and antibody detection and polymerase chain reaction (PCR) in patients with and without concurrent human immunodeficiency virus infection. Areas of agreement This includes recently developed fungal lateral flow assays, which have a low cost and operator skill requirement that give them great applicability to low-resource settings. Antigen detection for Cryptococcus, Histoplasma and Aspergillus spp. are much more sensitive than culture. PCR for Candida spp., Aspergillus spp., Mucorales and Pneumocystis jirovecii is more sensitive than culture and usually faster. Areas of controversy Effort must be made to utilize recent developments in fungal diagnostics in clinical settings outside of specialist centres and integrate their use into standard medical practice. Given the clinical similarities of the conditions and frequent co-infection, further study is required into the use of serological and molecular fungal tests, particularly in patients being treated for tuberculosis. Growing points Further study is needed to clarify the utility of these tests in low-resource settings confounded by a high prevalence of tuberculosis. Areas timely for developing research The diagnostic utility of these tests may require revision of laboratory work flows, care pathways and clinical and lab coordination, especially for any facility caring for the immunosuppressed, critically ill or those with chronic chest conditions, in whom fungal disease is common and underappreciated.