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Peer-Reviewed Journal Tracking and Analyzing Disease Trends pages 1101-1284 EDITOR-IN-CHIEF D. Peter Drotman Associate Editors EDITORIAL BOARD Paul Arguin, Atlanta, Georgia, USA Dennis Alexander, Addlestone, Surrey, UK Charles Ben Beard, Ft. Collins, Colorado, USA Timothy Barrett, Atlanta, Georgia, USA Ermias Belay, Atlanta, Georgia, USA Barry J. Beaty, Ft. Collins, Colorado, USA David Bell, Atlanta, Georgia, USA Martin J. Blaser, New York, New York, USA Sharon Bloom, Atlanta, GA, USA Christopher Braden, Atlanta, Georgia, USA Mary Brandt, Atlanta, Georgia, USA Arturo Casadevall, New York, New York, USA Corrie Brown, Athens, Georgia, USA Kenneth C. Castro, Atlanta, Georgia, USA Charles H. Calisher, Ft. Collins, Colorado, USA Louisa Chapman, Atlanta, Georgia, USA Michel Drancourt, Marseille, France Thomas Cleary, Houston, Texas, USA Paul V. Effler, Perth, Australia Vincent Deubel, Shanghai, China David Freedman, Birmingham, Alabama, USA Ed Eitzen, Washington, DC, USA Peter Gerner-Smidt, Atlanta, Georgia, USA Daniel Feikin, Baltimore, Maryland, USA Stephen Hadler, Atlanta, Georgia, USA Anthony Fiore, Atlanta, Georgia, USA Nina Marano, Nairobi, Kenya Kathleen Gensheimer, College Park, MD, USA Martin I. Meltzer, Atlanta, Georgia, USA Duane J. Gubler, Singapore David Morens, Bethesda, Maryland, USA Richard L. Guerrant, Charlottesville, Virginia, USA J. Glenn Morris, Gainesville, Florida, USA Scott Halstead, Arlington, Virginia, USA Patrice Nordmann, Fribourg, Switzerland Katrina Hedberg, Portland, Oregon, USA Didier Raoult, Marseille, France David L. Heymann, London, UK Pierre Rollin, Atlanta, Georgia, USA Charles King, Cleveland, Ohio, USA Ronald M. Rosenberg, Fort Collins, Colorado, USA Keith Klugman, Seattle, Washington, USA Frank Sorvillo, Los Angeles, California, USA Takeshi Kurata, Tokyo, Japan David Walker, Galveston, Texas, USA S.K. Lam, Kuala Lumpur, Malaysia Stuart Levy, Boston, Massachusetts, USA Senior Associate Editor, Emeritus John S. MacKenzie, Perth, Australia Brian W.J. Mahy, Bury St. Edmunds, Suffolk, UK Marian McDonald, Atlanta, Georgia, USA Managing Editor John E. McGowan, Jr., Atlanta, Georgia, USA Byron Breedlove, Atlanta, Georgia, USA Jennifer H. McQuiston, Atlanta, Georgia, USA Tom Marrie, Halifax, Nova Scotia, Canada Copy Editors Claudia Chesley, Laurie Dieterich, Karen Foster, Philip P. Mortimer, London, UK Thomas Gryczan, Jean Michaels Jones, Shannon O’Connor, Fred A. Murphy, Galveston, Texas, USA Rhonda Ray, Carol Snarey, P. Lynne Stockton Barbara E. Murray, Houston, Texas, USA Production William Hale, Aaron Moore, Barbara Segal, P. Keith Murray, Geelong, Australia Reginald Tucker Stephen M. Ostroff, Silver Spring, MD, USA Gabriel Rabinovich, Buenos Aires, Argentina Editorial Assistant Jared Friedberg Mario Raviglione, Geneva, Switzerland Communications/Social Media Sarah Logan Gregory David Relman, Palo Alto, California, USA Connie Schmaljohn, Frederick, Maryland, USA Founding Editor Tom Schwan, Hamilton, Montana, USA Joseph E. McDade, Rome, Georgia, USA Ira Schwartz, Valhalla, New York, USA Emerging Infectious Diseases is published monthly by the Centers for Disease Tom Shinnick, Atlanta, Georgia, USA Control and Prevention, 1600 Clifton Road, Mailstop D61, Atlanta, GA 30333, Bonnie Smoak, Bethesda, Maryland, USA USA. Telephone 404-639-1960, fax 404-639-1954, email [email protected]. Rosemary Soave, New York, New York, USA P. 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Use of trade names is for identification only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health ∞ Emerging Infectious Diseases is printed on acid-free paper that meets the requirements and Human Services. of ANSI/NISO 239.48-1992 (Permanence of Paper) Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 July 2015 On the Cover Transdermal Diagnosis of Malaria Using Vapor Nanobubbles ..........1122 Marianne North (1830–1890) E. Lukianova-Hleb et al. Foliage, Flowers, and Our laser device rapidly and noninvasively Seed-vessels of a Peruvian Bark Tree (1870s) detected malaria in a patient and identified parasite-positive mosquitoes. Oil on card 20 x 11.5 in / 50.8 x 29.2 cm Lack of Transmission among Image copyright Close Contacts of Patient with © Royal Botanic Gardens Kew Case of Middle East Respiratory Syndrome Imported into the About the Cover p. 1280 United States, 2014 ...................1128 Synopsis L. Breakwell et al. Despite 61 contacts with unprotected exposure, no secondary cases occurred. Monitoring of Ebola Virus Makona Disseminated Infections Evolution through Establishment of with Talaromyces marneffei p. 1105 Advanced Genomic Capability in Non-AIDS Patients Given in Liberia ...................................1135 Monoclonal Antibodies against CD20 and Kinase J.R. Kugelman et al. Inhibitors ......................1101 The effects of EBOV evolution on diagnostic J.F.W. Chan et al. assays and therapeutic drugs appear to be low. Clinicians should be aware of these infections, especially in patients from disease- endemic areas. Parechovirus Genotype 3 Research Outbreak among Infants, New South Wales, Australia, Macacine Herpesvirus 1 in 2013–2014....................1144 Long-Tailed Macaques, Malaysia, p. 1123 G. Cumming et al. 2009–2011 ................................1107 Syndromic surveillance was useful for outbreak M.-H. Lee et al. monitoring, and public health response helped Virus shedding by 39% of wild-caught reduce hospitalization times. macaques creates potential occupational risk for humans. MERS-CoV in Upper Respiratory Tract and Lungs of Dromedary Camels, Malaria Prevalence among Young Saudi Arabia, 2013–2014 .........1153 Infants in Different Transmission A.I. Khalafalla et al. Settings, Africa ..........................1114 Wide circulation among camels, especially S.J. Ceesay et al. during cooler months, is confirmed. Preventive measures and treatment guidelines are needed to address the sizeable prevalence of disease in this population. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 Assessment of Arbovirus Surveillance 13 Years after Introduction of West Nile Virus, United States ...1159 July 2015 J.L. Hadler et al. 1205 Detection of Circovirus Many states cannot rapidly detect and respond in Foxes with to this virus and other emerging arboviral threats. Meningoencephalitis, United Kindom, 2009–2013 Results from the National Legionella Outbreak Detection Program, S. Bexton et al. the Netherlands, 2002–2012 .....1167 1209 Determination of J.W. Den Boer et al. Predominance of Influenza The National Legionella Outbreak Detection Virus Strains in the Americas Programme (2002–2012) has provided new E. Azziz-Baumgartner et al. insights into Legionnaires’ disease patients in the Netherlands. 1213 Novel Arenavirus Isolates from Namaqua Rock Mice, Namibia, Seroprevalence for Hepatitis E and Southern Africa Other Viral Hepatitides in Diverse P.T. Witkowski et al. Populations, Malawi ...................1174 T.E. Taha et al. 1217 Readability of Ebola Analysis of blood samples from diverse p. 1139 Information on Websites of populations during approximately 20 years Public Health Agencies, suggests underestimation of hepatitis E virus United States, United Kingdom, Canada, Australia, and Europe in this country. E. Castro-Sánchez et al. Policy Review 1220 Evaluation of Patients under Investigation for MERS-CoV Chronic Q Fever Diagnosis— Infection, United States, Consensus Guideline versus January 2013–October 2014 Expert Opinion ..........................1183 E. Schneider et al. L.M. Kampschreur et al. Literature-based consensus guideline is more 1224 Wildlife Reservoir for sensitive and easier to use in clinical practice. Hepatitis E Virus, Southwestern France S. Lhomme et al. Dispatches p. 1150 1227 Asymptomatic Malaria and 1189 Swine Influenza A(H3N2) other Infections in Children Virus Infection in an Adopted from Ethiopia, Immunocompromised Man, United States, 2006–2011 Italy, 2014 S.M. Adebo et al. A. Piralla et al. 1230 Distinct Lineages of Bufavirus 1192 Severe Pediatric Adenovirus 7 in Wild Shrews and Disease in Singapore Linked to Nonhuman Primates Recent Outbreaks across Asia M. Sasaki et al. O.T. Ng et al. 1234 Geographic Range Expansion 1197 Hemagglutinin Receptor for Rat Lungworm in Binding of a Human Isolate of North America Influenza A(H10N8) Virus E.M. York et al. I. Ramos et al. 1237 Slow Clearance of Plasmodium 1202 Schmallenberg Virus falciparum in Severe Pediatric Reoccurrence, Germany 2014 Malaria, Uganda, 2011–2013 K. Wernike et al. M. Hawkes et al. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 1262 Characterization of 3 Megabase-Sized July 2015 Circular Replicons from Vibrio cholerae 1240 Gastroenteritis Outbreaks Caused by Norovirus GII.17, 1264 Severe Malaria not Guangdong Province, China, Responsive to Artemisinin 2014–2015 Derivatives in Man Returning from Angola to Vietnam J. Lu et al. 1266 Diversity of Bartonella spp. in 1243 Ebola Virus Stability on Bats, Southern Vietnam Surfaces and in Fluids in Simulated Outbreak 1267 Seropositivity for Avian Environments Influenza H6 Virus among R. Fischer et al. Humans, China 1247 Outbreak of Ciprofloxacin- 1269 Absence of MERS-Coronavirus Resistant Shigella sonnei in Bactrian Camels, Southern Associated with Travel to p. 1155 Mongolia, November 2014 Vietnam, South Korea J.S. Kim et al. 1271 Oligella ureolytica Bacteremia in Elderly Woman, 1251 Rapidly Expanding Range United States of Highly Pathogenic Avian Influenza Viruses 1273 Estimating Ebola Treatment J.S. Hall et al. Needs, United States 1253 Cluster of Ebola Virus 1275 Highly Pathogenic Avian Disease, Bong and Influenza A(H5N1) Virus in Montserrado Counties, Poultry, Nigeria, 2015 Liberia p. 1200 Books and Media T.G. Nyenswah et al. 1278 Pulmonary Complications Another Dimension of HIV 1257 The Past Is Never Dead— 1278 The Emergence of Tropical Measles Epidemic, Boston, Medicine in France Massachusetts, 1713 D.M. Morens About the Cover 1280 Portrait of the Letters Coveted Cinchona 1261 Influenza A(H5N6) Etymologia Virus Reassortant, 1127 Quinine Southern China, 2014 Correction 1279 Vol 21, No. 3 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 Presenting the ongoing challenges that emerging microbial threats pose to global health SYNOPSIS Disseminated Infections with Talaromyces marneffei in Non-AIDS Patients Given Monoclonal Antibodies against CD20 and Kinase Inhibitors Jasper F.W. Chan, Thomas S.Y. Chan, Harinder Gill, Frank Y.F. Lam, Nigel J. Trendell-Smith, Siddharth Sridhar, Herman Tse, Susanna K.P. Lau, Ivan F.N. Hung, Kwok-Yung Yuen, Patrick C.Y. Woo Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit. This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint providership of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at http://www.medscape.org/journal/eid; (4) view/print certificate. Release date: June 15, 2015; Expiration date: June 15, 2016 Learning Objectives Upon completion of this activity, participants will be able to: 1. Distinguish the clinical and epidemiologic characteristics of T. marneffei infection, based on a case series report 2. Discuss the recent emergence of disseminated T. marneffei infection in non-AIDS patients with hematologic malignant neoplasms treated with targeted therapies 3. Identify possible mechanisms of action underlying disseminated T. marneffei infection in non-AIDS patients with hematologic malignant neoplasms treated with targeted therapies CME Editor Thomas J. Gryczan, MS, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Thomas J. Gryczan, MS, has disclosed no relevant financial relationships. CME Author Laurie Barclay, MD, freelance writer and reviewer, Medscape, LLC. Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships. Authors Disclosures: Harinder Gill, MBBS; Frank Y.F. Lam, MBBS, MRCP(UK), FHKAM; Nigel J. Trendell-Smith, MBBS, FRCPath; Siddharth Sridhar, MBBS, MRCP(UK); Herman Tse, MBBS; Susanna K.P. Lau, MD; and Kwok-Yung Yuen, MD, have disclosed no relevant financial relationships. Jasper F.W. Chan, MBBS, FRCPath, FRCP(Edin), has disclosed the following relevant financial relationships: received travel grants from Pfizer Co. HK Ltd. and Astellas Pharma HK Co. Ltd. Thomas S.Y. Chan, MBBS(Hons), MRCP(UK), FHKAM(Med), has disclosed the following relevant financial relationships: served as a speaker or a member of a speakers bureau for Pfizer. Ivan F.N. Hung, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Pfizer (Asia Pacific Capital Advisory Board), MSD; received conference sponsorships from AstraZeneca, Ferring. Patrick C.Y. Woo, MD, has disclosed the following relevant financial relationships: involved in Tigecycline Evaluation Surveillance Trial with Pfizer. Aut hor affiliation: The University of Hong Kong, Hong Kong, China DOI: http://dx.doi.org/10.3201/eid2107.150138 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 1101 SYNOPSIS Infections with the fungus Talaromyces (formerly Penicillium) mycophenolate sodium. A chest radiograph showed a small marneffei are rare in patients who do not have AIDS. We cavitary lesion in the right lower lobe. His symptoms and report disseminated T. marneffei infection in 4 hematology signs did not resolve after he received empirical intrave- patients without AIDS who received targeted therapy with nous imipenem/cilastatin and metronidazole (Table 2). monoclonal antibodies against CD20 or kinase inhibitors A colonoscopy showed multiple shallow ulcers at the during the past 2 years. Clinicians should be aware of this terminal ileum (Figure 1). Histologic analysis of an ulcer emerging complication, especially in patients from disease- biopsy specimen showed slough of an acutely inflamed ul- endemic regions. cer but no microorganisms. However, histologic analysis of a specimen from a nasopharyngeal biopsy performed Talaromyces (formerly Penicillium) marneffei is a for persistent left facial pain showed abundant yeast cells pathogenic, thermal dimorphic fungus that causes sys- engulfed by foamy macrophages (Figure 2). Culture of temic mycosis in Southeast Asia. T. marneffei infection is terminal ileal ulcer biopsy specimens, stool samples, and characterized by fungal invasion of multiple organ systems, nasopharyngeal biopsy specimens yielded T. marneffei. especially blood, bone marrow, skin, lungs, and reticulo- A contrast-enhanced cranial computed tomography (CT) endothelial tissues, and is highly fatal, especially when scan showed 2 lesions (3–4-mm) with rim enhancement diagnosis and treatment are delayed (1,2). This disease is and perifocal edema at the right occipital and left parieto- found predominantly in AIDS patients and occasionally occipital lobes. A thoracic CT scan showed 2 cavitary le- those with cell-mediated immunodeficiencies involving sions (4–8 mm) in the right upper and lower lobes. the interleukin-12/interferon-γ (IFN-γ) signaling pathway, Immunologic testing showed that the patient was nega- such as congenital STAT1 mutations or acquired autoanti- tive for HIV and autoantibodies against IFN-γ. His CD3+ bodies against IFN-γ (1,3–6). The infection has rarely been and CD8+ counts were within references ranges, but he had reported among hematology patients, including those from mild CD4+ lymphopenia (Table 2). His fever and symptoms disease-endemic regions (7,8). resolved with after 2 weeks of treatment with intravenous At Queen Mary Hospital in Hong Kong, a 1,600-bed liposomal amphotericin B, followed by oral voriconazole. university teaching hospital that has a hematopoietic stem Reassessment colonoscopy (at 2 months) and CT scan (at 6 cell transplantation service, where a wide range of inva- months) showed complete resolution of all lesions. sive fungal infections have been observed (9,10), only 3 cases of T. marneffei infection were encountered in >2,000 Case-Patient 2 hematology patients in the past 20 years, despite the long- Patient 2 was a 44-year-old Chinese man who had fever standing availability of mycologic culture and serologic for 2 days. He had previously received chemotherapy and testing (7,8,11,12). In contrast, the infection was common- mAbs against CD20 (rituximab, 14 months earlier; obinu- ly reported among AIDS patients (13). tuzumab, concomitant) for refractory chronic lymphocytic In the past 2 years, we have been alerted by 4 unprece- leukemia (CLL) involving bone marrow (Table 1). He was dented cases of disseminated T. marneffei infection among empirically given intravenous piperacillin/tazobactam and non-AIDS hematology patients given targeted therapies, anidulafungin (Table 2). Histologic analysis of a trephine including monoclonal antibodies (mAbs) against CD20 biopsy specimen showed persistent CLL with plasmacytic and kinase inhibitors, which are being increasingly used differentiation, and Grocott staining showed yeasts with in recent years. We report details for these 4 hematology central septa in small clusters. Culture of peripheral blood case-patients. The study was approved by the institutional and bone marrow aspirate yielded T. marneffei. A change review board of The University of Hong Kong/Hospital in antifungal treatment to intravenous amphotericin B led Authority Hong Kong West Cluster in Hong Kong. to defervescence and clearance of fungemia. He was given oral itraconazole as maintenance therapy. He remained Case-Patient 1 well until 2 months later when he was hospitalized for Patient 1 was a 56-year-old Filipino man with Walden- deteriorating CLL complicated by neutropenic fever with ström macroglobulinemia, idiopathic thrombocytope- multiorgan failure caused by other opportunistic infections nic purpura, and primary biliary cirrhosis. He had fever, (Table 1). He died 5 months after the episode of dissemi- night sweating, productive cough, and left facial pain for nated T. marneffei infection. 1 week and bloody diarrhea for 2 days. He had previously received fludarabine, dexamethasone, and rituximab (mAb Case-Patient 3 against CD20, 18 months earlier) for treatment of Walden- Patient 3 was a 63-year-old Chinese man with myelofibro- ström macroglobulinemia (Table 1). The idiopathic sis and well-controlled diabetes mellitus. He had intermit- thrombocytopenic purpura was controlled with intrave- tent fever, right cervical lymphadenopathy, and produc- nous immunoglobulin and maintenance prednisolone and tive cough for 4 months. He was given ruxolitinib (kinase 1102 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 Disseminated Infections with Talaromyces marneffei Table 1. Characteristics of 4 case-patients with disseminated Talaromyces marneffei infection after targeted therapies* Characteristic Case-patient 1 Case-patient 2 Case-patient 3 Case-patient 4 Age, y/sex 56/M 44/M 63/M 67/M Concurrent conditions Waldenström Chronic lymphocytic Myelofibrosis with Acute myeloid leukemia, macroglobulinemia, leukemia splenectomy, hypertension idiopathic diabetes mellitus thrombocytopenic purpura, primary biliary cirrhosis Targeted therapy Rituximab Rituximab and Ruxolitinib Sorafenib obinutuzumab Action of therapy mAb against CD20 mAb against CD20 JAK-1/2 inhibitor Multikinase inhibitor Time interval, mo† 18 14 (rituximab) and Concomitant Concomitant concomitant (obinutuzumab) Cumulative dose before 700 mg/dose iv 700 mg/dose IV x 13 10–20 mg 2/d oral 400 mg 2/d oral x 8 mo T. marneffei infection x 4 doses doses (rituximab) and x 6.5 mo 1,000 mg IV x 3 doses (obinutuzumab) Other Fludarabine and Fludarabine and None Mitoxantrone and immunosuppressants dexamethasone (39), cyclophosphamide (48), etoposide (21), (time interval, mo)† prednisolone 10 mg/d CHOP (36), daunarubicin (20), and mycophenolate bendamustine (13) clofarabine (18), sodium 360 mg 2/d azacitidine (15), (concomitant) decitabine (15), cytarabine (14) Clinical manifestations Terminal ileitis, Marrow infiltration Right cervical Fungemia cerebral abscesses, and fungemia lymphadenitis and nasopharyngitis, multiple cavitary and multiple cavitary lung lesions lung lesions Specimens positive for Feces, and terminal ileal Blood and bone Right cervical Blood T. marneffei and nasopharyngeal marrow aspirate lymph node biopsy specimens Highest serum antibody 1:320 <1:40 1:320 <1:40 titer against T. marneffei Antifungal treatment Amphotericin B (2 Amphotericin B (2 Amphotericin B (2 Amphotericin B (2 (duration, mo) weeks) and weeks) and weeks) and weeks) and voriconazole (>21) itraconaozle (5) voriconazole (>6) voriconazole (>5) Other opportunistic None Bacteremia Bacteremia Herpes zoster infections (Mycobacterium (Klebsiella pneumoniae) at right occiput chelonae, Enterococcus faecium, and MRCNS), fungemia (Candida glabrata), HSV oral mucositis, PJP Clinical outcome Responded to Clearance of T. marneffei Responded to Responded to antifungal treatment fungemia but died of antifungal treatment antifungal treatment MODS and multiple infections 5 mo after T. marneffei infection *mAb, monoclonal antibody; JAK, Janus kinase; IV, intravenous; CHOP, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone; MRCNS, methicillin-resistant coagulase-negative Staphylococcus; HSV, herpes simplex virus; PJP, Pneumocystis jiroveci pneumonia; MODS, multiple organ dysfunction syndrome. †Time interval between end of therapy and onset of symptoms for T. marneffei infection. inhibitor) 6 months before symptom onset because of resolved after treatment with intravenous amphotericin B transfusion-dependent myelofibrosis despite splenectomy 4 for 2 weeks, followed by oral voriconazole for 6 months. years earlier (Table 1). A chest radiograph and thoracic CT scan showed multiple cavitary lesions and consolidation. Case-Patient 4 Bronchoalveolar lavage was negative for bacteria, fungi, Patient 4 was a 67-year-old Chinese man with acute my- and mycobacteria. A serum cryptococcal antigen test re- eloid leukemia and hypertension. He had fever and mal- sult was negative. He was empirically given intravenous aise for 2 days without localizing signs. He had been given imipenem/cilastatin and oral doxycycline, but his symp- sorafenib (kinase inhibitor) 8 months earlier for chemother- toms persisted. A right cervical lymph node culture yielded apy-refractory acute myeloid leukemia (Table 1). His fever T. marneffei. His symptoms and radiologic abnormalities did not respond to intravenous meropenem. Subsequently, Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015 1103 SYNOPSIS Table 2. Laboratory results for 4 case-patients with disseminated Talaromyces marneffei infection after targeted therapies* Laboratory parameter Case-patient 1 Case-patient 2 Case-patient 3 Case-patient 4 Hematologic† Leukocytes, x 109 cells/L 12.08 0.91 4.93 33.79 Neutrophils, x 109 cells/L 11.01 0.45 3.11 8.45 (with blasts) Lymphocytes, x 109 cells/L 0.83 (CD4+: 315/µL)‡ 0.45 1.05 9.12 (with blasts) Hemoglobin, g/dL 12.3 10.3 8.0 9.2 Platelets, x 109/L 250 5 539 15 Biochemical† Sodium, mmol/L 136 135 139 138 Potassium, mmol/L 3.5 4.1 3.7 4.4 Creatinine, µmol/L 101 111 78 92 Albumin, g/L 40 32 39 37 Globulin, g/L 34 36 36 39 Total bilirubin, µmol/L 8 9 13 19 ALP, U/L 234 163 112 96 ALT, U/L 79 20 32 61 AST, U/L 38 9 28 123 LDH, U/L 209 97 352 2,069 Immunologic Combined HIV antibody/antigen Negative Negative Negative Negative Autoantibody against IFN-γ Negative Negative Negative Negative Microbiologic Blood culture No bacteria and fungi T. marneffei; Klebsiella T. marneffei Mycobacterium pneumoniae§ chelonae, Enterococcus faecium, MRCNS, and Candida glabrata§ Bone marrow aspirate ND T. marrneffei ND ND Sputum culture Negative for pathogenic Negative for Negative for Negative for bacteria, AFB, and fungi pathogenic pathogenic bacteria, pathogenic bacteria, bacteria, AFB, and AFB, and fungi AFB, and fungi fungi Urine culture No bacteria and fungi No bacteria and No bacteria and fungi No bacteria and fungi fungi Stool culture T. marneffei; negative ND ND ND for pathogenic bacteria, including Clostridium difficile and AFB Serum CMV pp65 antigen Negative Negative Negative Negative Other Stool for C. difficile toxin BAL: Pneumocystis Cervical lymph node: T. (negative); serum for jiroveci (smear- marneffei (culture- Entamoeba histolytica positive) positive) antibody (negative); multiple blood smears for Plasmodium sp. (negative) *ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; LDH, lactate dehydrogenase; IFN-γ, interferon-γ; MRCNS, methicillin-resistant coagulase-negative Staphylococcus; ND, not done; AFB, acid-fast bacilli; CMV, cytomegalovirus; BAL, bronchoalveolar lavage. Reference ranges: leukocytes; 3.89–9.93 × 109 cells/L; neutrophils, 2.01–7.42 × 109 cells/L; lymphocytes, 1.06–3.61 × 109 cells/L; hemoglobin, 13.3– 17.7g/dL; platelets, 162–341 × 109/L; sodium, 136–148 mmol/L; potassium, 3.6–5.0 mmol/L; creatinine, 67–109 µmol/L; albumin, 39–50 g/L; globulin, 24– 37 g/L; total bilirubin, 4–23 µmol/L; ALP, 42–110 U/L; ALT, 8–58 U/L; AST, 5–38 U/L; LDH, 118–221 U/L. †Results at presentation. ‡Reference range of CD4+ lymphocyte count: 415–1,418 cells/µL. §Bacteremia caused by M. chelonae, E. faecium, MRCNS, and candidemia in case-patient 2, and bacteremia caused by K. pneumoniae in case-patient 3 occurred after recovery from T. marneffei infection and prolonged hospitalization. 2 sets of blood cultures yielded T. marneffei. He was given T. marneffei infection has rarely been seen in non-AIDS intravenous amphotericin B for 2 weeks, followed by oral patients, even in disease-endemic regions. During 1994– voriconazole. He remained well at follow-up 6 months af- 2014, only 3 other cases were observed in our hematol- ter symptom onset. ogy patients (7,8,11). None of 47 patients with T. marneffei infection in another large local case series during Discussion 1994–2004 had hematologic disease (13). In the past 20 T. marneffei infection is an emerging complication in he- years, there has been no change in methods for laboratory matology patients receiving targeted therapies. Historically, diagnosis of T. marneffei infection or a marked increase 1104 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 21, No. 7, July 2015