MYCOTIC INFECTIONS in the MIDDLE EAST (Basidiobolus and Rhinocladiella)
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MYCOTIC INFECTIONS IN THE MIDDLE EAST (Basidiobolus and Rhinocladiella) Ziauddin Khan, PhD Professor of Medical Mycology Department of Microbiology Faculty of Medicine Kuwait University Basidiobolus and Basidiobolomycosis TAXONOMICAL CONSIDERATIONS Zygomycota underwent major taxonomic changes in 2007. Hibbet and others proposed to eliminate Zygomycota and the taxa conventionally placed in Zygomycota were distributed among the phylum Glomeromycota. Mucorales and Entomophthorales, which contain zoopathogenic fungi, and 2 other orders including Kickxellales and Zoopagales were raised to the rank of subphyla: Mucoromycotina, Entomophthoromycotina, Kickxellomycotina and Zoopagomycotina. TAXONOMIC CLASSIFICATION OLD NEW Kwon-Chung Clin Infect Dis. 2012;54:S8-S15 A proposed new classification schemes of the kingdom Fungi Basidiobolomycetes Neozygitomycetes Entomophothoromycetes Basidiobolus spp. Neozygitis spp. Conidiobolus spp. Humber, 2012 Phylogenetic classification of entomophthoroid fungi Phylum: Entomophthoromycota Class: Basidiobolomycetes Order: Basidiobolales Family: Basidiobolaceae Genus: Basidiobolus Gryganskyi et al. Persoonia 2013; 30;94-105. Maximum likelihood phylogeny of Basidiobolomycotina (secondary conidiogenesis) Basidiobolus and the still formally undescribed genera Schizangiella and Drechslerosporium (LSU, SSU, RPB2, mtSSU, ITS). Gryganskyi et al. Persoonia 2013; 30;94-105 Life Cycle of Adapted from Mendoza et al. 2015 Basidiobolus ranarum in intestinal tract of bats, reptiles and amphibians Intestinal contents of 14 (7%) of 200 bats belonging to Rhinopoma hardwickei hardwickei Gray ('the lesser rat- tailed bat'), an insectivorous species captured from Delhi area. Chaturvedi et al. Sabouraudia. 1984;22:185-9. Intestinal tract of 50% of trapped reptiles and amphibians from Florida were found colonized with a Basidiobolus species. Okafor et al. Sabouraudia. 1984;22:47-51. Epidemiology • Most cases of basidiobolomycosis have been reported from tropical and subtropical regions of Africa, South America, and Asia • It usually causes subcutaneous infections • Infections caused by B. ranarum are mainly diagnosed in children (80% under the age of 20 years) with a male/female ratio of 3:1. • B. ranarum also causes chronic granulomatous infection of the gastrointestinal tract in apparently immunocompetent patients, mostly from Arizona (USA) and Middle East Basidiobolus is a ubiquitous fungus The majority of cases have been reported in South America, Africa and tropical Asia. However, recently this fungus has been classified as an emerging invasive fungal infection in desert regions of the US Southwest and Middle East causing gastrointestinal basidiobolomycosis. Basidiobolomycosis: Clinical types Subcutaneous “Bathing suit distribution” Gastrointestinal Colorectal involvement Complications: Small bowel, Liver, Gall bladder, Kidney, Pancreas, other intraabdominal organs Clinical Manifestations: Basidiobolomycosis The presenting feature is a single painless, unilateral, well-circumscribed subcutaneous mass that usually affects the buttock or the thigh but can also be seen in the arm, the neck, the face or the trunk. The disease starts as a single nodule that progressively grows. The swelling is often described as woody and hard. The swelling over thigh in an 18-month-old female of three months duration caused by Basidiobolus ranarum (culture and histopathology proven). Treated with KI (3 times a day) and lesion resolved within 1 month Naniwadekar et al. 2009 A case from Karad, Karnataka Induration and multiple nodules in the Buttock (toilet leaves?) perineum and labia (biopsy site seen) Radjou & Rajesh Ind J Microbiol. 2011; 29:186-188 A case fro Puducherry Histopathology Chronic inflammatory process can be seen with small abscesses surrounded by a granulomatous tissue reaction. A strong eosinophilic perihyphal reaction is often observed (Splendore-Hoeppli phenomenon) that is variable in size (2-6 µm). Board irregular hyphae (4-30µm) with thin walls and rare septation can be seen, singly or in clusters. There is no invasion of blood vessels or infection of tissue. Splendore-Hoeppli phenomenon (H &E) and Broad, aseptate hyphal fragments (GMS) CULTURE Biopsy specimen should be cultured immediately as B. ranarum dies quickly in tissues kept in a refrigerator. Tissue biopsy should be minced and not homogenized. Homogenization in a tissue grinder should be avoided, because it decreases culture yield by destroying hyphae. SDA with antibiotics can be used. Cycloheximide should not be used in SDA. Incubation at 25°-30° C for 2-5 days. Gastrointestinal Basidiobolomycosis CASE 1: A 30-year-old Bangladeshi with rectal bleeding • Rectal mass ~10 cm large polypoid mass on lower third of rectum • Provisional diagnosis: Piles, rectal carcinoma • First biopsy: epithelioid cell granuloma infiltrated with eosinophils- Crohn’s disease Histopathology: Fungal elements were missed • Second biopsy: Histopathology: Fungal elements missed, culture yielded a fungus Khan et al. Clin Infect Dis. 1998;26:521-3 B. ranarum colonies on SDA Khan et al. Clin Infect Dis 1998;26:521 Zygospores Immunodiffusion test Case 2: A 41-year-old Indian male with history of repair of a left inguinal hernia • Examination: palpable, nodular mass near rt. hypochondrium, • Ultrasound: thickening of ascending colon and cecum and renal involvement • Provisional diagnosis: Intestinal tuberculosis Khan et al. J Clin Microbiol. 2001 ;39:2360-3 Hematoxylin-and-eosin-stained section An open segment of large intestine of intestinal mucosa showing a cross showing a thick-walled mucosa with a section of a B. ranarum hypha (arrow) cobblestone appearance mimicking surrounded by the Splendore-Hoeppli Crohn's disease phenomenon and many eosinophils KOH-calcofluor white mount showing broad, non- septate, branched hyphae in urine sediment The isolate was resistant to Amphotericin B (4 µg/ml) and itraconazole (8 µg/ml) Serodiagnosis Ag Ab-I Ab-II Ag-whole cell homoginate; patients’ sera Ab-I and Ab-II A case from Yemen/SA A 12-year-old Yemeni boy, living in Saudi Arabia, was referred with a 2-month history of diffuse abdominal pain, non-bilious vomiting, poor appetite and weight loss. percutaneous liver biopsy under ultrasound guidance and sent for histopathological evaluation, which revealed granulomatous lesions rich in eosinophils with broad aseptate fungal hyphae surrounded by eosinophilic material (Splendore–Hoeppli phenomenon). Saeed et al. JMM CR 2014 Abdominal CT showing multiple small, low-attenuation lesions scattered throughout both lobes of the liver, some showing ring enhancement Saeed et al. JMM CR 2014 Liver CT after treatment with itraconazole treatment. Complete resolution after 12 months. Saeed et al. JMM CR 2014 A case from Iran Gastrointestinal basidiobolomycosis accompanied by liver Involvement Gross Pathology of the Granuloma, Eosinophilic Infiltration and Terminal Ileum and Right Splendore-Hoeppli Phenomenon (Arrow) Colon Shows Ulceration in the Cecum (Arrow) A 41-year-old lady from Shiraz, south of Iran. CT-scan of the abdomen and pelvic showed increased thickness of the cecum with infiltrative process and hypoattenuating lesions in the liver, supporting liver abscesses or metastasis with central necrosis Diagnosis was based on histopathologic observation and response to itraconazole therapy (200 mg twice a day for 4 months) Ejtehadi et al. Iran Red Crescent Med J. 2014; 16: e14109. A case from Saudi Arabia Gastrointestinal basidiobolomycosis with liver Involvement A 24-year-old woman from Saudi Arabia with type I diabetes mellitus presented to the emergency department with a 4-day history of severe abdominal pain, nausea, vomiting, abdominal distension, and constipation. Magnetic resonance imaging of the abdomen showed 2 long segments of circumferential heterogeneous enhancing soft tissue masses involving the descending colon and descending sigmoid colon Lactophenol cotton blue stain of and multiple different-size hepatic growth from fine needle aspiration lesions. Isolate identified by D1/D2 material from the liver lesion, X400 sequencing. Treated with voriconazole. Alhuraiji et al. Clin Infect Dis. 2014; 58:990 Eosinophilic granulomatous gastrointestinal and hepatic abscesses attributable to basidiobolomycosis in Iraqi Kurdistan (2009-2012) - All males (6 cases) - Age: 17 months -59 years - Sites affected: Cecum and/or colon-5 cases, oropharyngeal and transverse colon mass-1 - Diagnosis- Histopathological (sparsely septate hyphae) - Treatment: oral itraconazole -5, all responded, became asymptomatic (4-6 months); - One (17 months old) died after 2days of start of amphotericin B Hassan et al. BMC Infect Dis. 2013; 13: 91. Characteristics of 72 Patients With Gastrointestinal Basidiobolomycosis Variables Value Age, years 13 months-81 years, ~85% in pediatric age group Male sex 59 (82%) Country of residence United States 19, 17 from Arizona Saudi Arabia 16, 14 in <12 years Iran 18, 11 <12 years n=42 Kuwait 2, Adults (Indian, Bangladeshi) Iraq/Kurdistan 6, 2 in< 12 years Brazil 4 Others 7 (Nigeria, Italy, Netherlands, UK, Egypt, Thailand) Onset of GIB 1964–1994 8 1995–2008 64 (86%) (Geramizadeh et al. 2012; Vikram et al. 2012; Al-Asmi et al. 2013) Antifungal susceptibilities of Conidiobolus and Basidiobolus Species Geometric mean MICs (mg/L) (no. of isolates Amphot Fluconaz Flucytosi Itracona Ketocon Miconaz tested) ericin B ole ne zole azole ole Conidiob olus spp. (9) 3.1 107.5 234.6 11.3 20.7 11.3 Basidiob olus spp. (8)* 2.7 14.8 165.9 1.8 1.0 3.9 *Voriconazole