Estimation of Serious Mycoses Burden in Indonesia

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This study estimates the burden of serious fungal infections in Indonesia, a country with rich biodiversity and limited medical mycology facilities. The data indicates a high prevalence of opportunistic infections in AIDS patients and TB cases, with Candidiasis and Cryptococcosis being significant concerns among different patient groups, especially those with HIV infections. The findings highlight the need for better management and prevention strategies for these fungal diseases in Indonesia.

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1 ESTIMATION OF THE BURDEN OF SERIOUS MYCOSES IN INDONESIA Retno Wahyuningsih 1Department of Parasitology, Universitas Indonesia, Faculty of Medicine, Jakarta, 5Department of Parasitology, Universitas Kristen Indonesia, School of Medicine, Jakarta,

Indonesia Tropical islands Rich biodiversity Pathogenic fungi

3 INDONESIA: A LARGE COUNTRY WITH 17.000 ISLANDS Medical mycology facilities limited in big cities

Source of data 4 Estimation of Indonesia fungal burden based on laboratory data, manuscripts, publications and the health profile 2013 (government) High number of AIDS patients: 52348, so that opportunistic infection in this group must be considered High number of TB cases

KOH slide- sputum 1. Candidiasis

Invasive Candidiasis 6 Prevalence of candidemia in neonates 63%, in adult 12.33% in leukemia children with fever 8% Candidemia prevalence in adults, children & neonates during 5 years: 12% (data Dept. Parasitology FKUI) Estimation of the candidemia prevalence in Indonesia in general 8 -12.3%, in neonates 63% specifically Causes: C. tropicalis, C. albicans & C. parapsilosis Concl.: the rate is 8 63 10-4/100 000 population Wahyuningsih et al Maj Kedok Indon 2008; Rusli, thesis 2013; Kalista, thesis 2015,

Candidosis HIV infection 7 Prevalence of oral candidiasis among HIV infected patient in Cipto Mangunkusumo hospital 50% in 2004 57% in 2014 The main cause is C. albicans, followed by C. tropicalis C. glabrata C. parapsilosis C. nivariensis C. ethanolica Concl.: 50-47 10-4/100 000 Wulandari et al. manuscript, Wahyuningsih et al. JCM 2008

2. Cryptococcosis India ink spinal fluid

Cryptococcosis HIV infection 9 Based on culture and microscopy of spinal fluid Prevalence among AIDS patients (2003-2014): Jakarta 16-26.8% Bandung 29.8% Based on cryptococcal serum antigen (CrAg) among ambulatory patient Jakarta 6.4% Bandung 7.1%. The highest prevalence in HIV infected patients with cerebral involvement ranges between 16-30 10-4/100 000 population

Cryptococcal meningitis among HIV infected patients in Jakarta, Indonesia Year 2003 n=2 2004 n=31 2005 n=13 2006 n=52 2007 n=89 20 08 n= 86 2009 n=124 2010 n=90 2011 n=103 2012 n= 108 2013 n=58 2014 n=67 Sex - 3 2 10 22 13 15 22 26 28 18 40 Female 2 28 11 42 67 73 109 68 77 80 40 27 Male Cryptococcus meningitis Female - - - 3 2 1 3 2 1 5 2 3 Male 2 3 3 8 16 19 18 17 15 24 8 12 n 2 3 3 11 18 20 21 19 16 29 10 15 - 3/28 2/13 21.15 20.22 23.25 16.93 21.1 15.53 26.85 17.24 25.37 Incidence (%)

Cryptococcosisnon HIV 11 Cryptococcosis was also detected in non HIV infected patient in Jakarta & Sumatera Patient with CD4 lymphocytopenia Lung tumors in a diabetic patient Skin infection in Hodgkin lymphoma Meningitis in mallnourished child Pericarditis in a child Adult with meningitis (2 patients) A male with bronchial problem

Cryptococcosis (AIDS): origin of cases 12 Riau Places where cryptococcosis were diagnosed; underestimate

Cryptococcus: the species-var 13 The most prevalent is C. neoformans var grubii Maldi-TOF analysis of isolates derived from HIV & non-HIV patients reveales: C. neoformans var. grubii : 265 isolates C. neoformans var neoformans: 6 isolates C. neoformans: 3isolates C. neoformans intervariety hybrid (AFLP3): 16 isolates C. neoformans var grubii x C. gattii (AFLP 9): 1 isolate Adawyah et al, manuscript, Khayhan et al. PlosOne 2012; Pan et al. PlosOne 2011

3. Aspergillosis Aspergillus head KOH wet slide

Aspergillosis 15 The prevalence of invasive pulmonary aspergillosis in critically ill patients Jakarta is 7.65% and mostly caused by A. flavus; ca. 8 10-4/100 000 population In the world, Indonesia is rank 4 for TB Regarding TB, WHO estimates in Indonesia (2013) the 1-year-post-treatment survivors : 1, 297 047 those develop chronic pulmonary aspergillosis : 26,935 Estimation based on statistical analysis, but in real? Rozaliyani et al, manuscript; WHO report on TB- Indonesia 2013

Post TB patient with chronic cavitary pulmonary aspergillosis Wahyuningsih et al., Advance Asp. Istanbul 2012

Aspergillus-susceptibility 17 Susceptibility study Resistant A. fumigatus SLE with retro-bulbair mass Aspergilloma Pulmonary mass Wahyuningsih et al., Advance Asp, Madrid 2014

4. Pneumocyctosis

Pneumocystosis 19 Pneumocystis jirovecii prevalence among 55 AIDS patients with pneumonia (PJP): 14.5%. co infection with TB Five-year prevalence data on the examination of induced sputum and broncho-alveolar lavage : 28% (HIV infected patient, COPD & ICU patients with lung disease) Prevention of PCP among HIV infected patients starts immediately after diagnosis makes determining prevalence of PCP difficult. Rozaliyani et al., thesis; data Dept. Parasitology FKUI

5. Histoplasmosis Result of touch biopsy: Cutaneous histoplasmosis

Histoplasmosis 21 Mostly male Before the arrival of AIDS pandemic, histoplasmosis was diagnosed in children and adult The increasing number of AIDS in Indonesia resulted an increase in the number of histoplasmosis cases Cutaneous and disseminated forms of histoplasmosis have been diagnosed in AIDS (last 10 years) and disseminated form in non HIV (since 1932)

Histoplasmosis 22 1953-55: histoplasmin skin test on 2542 people; positive in 2.7% in student of elementary school 9-12 % in adult (mostly male) Radiology on 2311 people: 1.5 % have pulmonary calcification (mostly male) Adult 1.5% with calcification Mostly in patients with tuberculin positive have histoplasmin positive Suggesting Indonesia as endemic area Joe et al., Am J Trop Med Hyg 1956; 5: 110; Joe et al., Berita Dep Kes RI. 1956; 5(3):132-34 Delima I. Medika 1988

Histoplamosis: clinical spectra 23 Hematology malignancy (bone marrow examination) Chronic lung disease Tuberculosis Carcinoma of the palate Ulcer Hepatitis Fever of unknown origin Skin infection (dissemination of systemic infection)

Cases of histoplasmosis 24 Java: Jakarta, Tanggerang, Bandung, Sukabumi, Jatibarang, Surabaya, Sumatera: Riau Celebes: Manado

6. Penicilliosis Culture of P. marneffei

Penicilliosis 26 Very limited data Diagnosed in 2 HIV infected patients A male with bronchomalacia using bronchial prosthesis Sinusitis 2 patients with lung disorders From one HIV infected patient, P. marneffei was isolated from the lung & liver of a (house) rat caught in his house. Source of infection in Jakarta?

Summary 27 Almost all serious mycoses is found in Indonesia These data does not describe the actual condition (underestimate) To address (2), it is necessary to spread diagnostic capabilities throughout the country Getting insight into Indonesia s fungal burden will help policy makers and clinicians making decisions in the absence of data 1. 2. 3. 4.

Collaborators 28 Indonesia England, The Netherlands J. Prihartono D. Denning R. Adawiyah: T. Boekhout R. Syam J. F.MG.Meis A. Rozaliyani Mulyati E. A. T. Wulandari D. Imran F. E. Siagian