High Mortality and Coinfection in a Prospective Cohort of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients with Histoplasmosis in Guatemala

Blanca Samayoa Clinica Familiar “Luis Ángel García,” Hospital General San Juan de Dios/Asociación de Salud Integral, Guatemala, Guatemala;
Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala, Guatemala;

Search for other papers by Blanca Samayoa in
Current site
Google Scholar
PubMed
Close
,
Monika Roy Centers for Disease Control and Prevention, Atlanta, Georgia;

Search for other papers by Monika Roy in
Current site
Google Scholar
PubMed
Close
,
Angela Ahlquist Cleveland Centers for Disease Control and Prevention, Atlanta, Georgia;

Search for other papers by Angela Ahlquist Cleveland in
Current site
Google Scholar
PubMed
Close
,
Narda Medina Clinica Familiar “Luis Ángel García,” Hospital General San Juan de Dios/Asociación de Salud Integral, Guatemala, Guatemala;

Search for other papers by Narda Medina in
Current site
Google Scholar
PubMed
Close
,
Dalia Lau-Bonilla Clinica Familiar “Luis Ángel García,” Hospital General San Juan de Dios/Asociación de Salud Integral, Guatemala, Guatemala;

Search for other papers by Dalia Lau-Bonilla in
Current site
Google Scholar
PubMed
Close
,
Christina M. Scheel Centers for Disease Control and Prevention, Atlanta, Georgia;

Search for other papers by Christina M. Scheel in
Current site
Google Scholar
PubMed
Close
,
Beatriz L. Gomez School of Medicine, Universidad del Rosario, Bogota, Colombia;
Corporación para Investigaciones Biológicas, Medellín, Colombia

Search for other papers by Beatriz L. Gomez in
Current site
Google Scholar
PubMed
Close
,
Tom Chiller Centers for Disease Control and Prevention, Atlanta, Georgia;

Search for other papers by Tom Chiller in
Current site
Google Scholar
PubMed
Close
, and
Eduardo Arathoon Clinica Familiar “Luis Ángel García,” Hospital General San Juan de Dios/Asociación de Salud Integral, Guatemala, Guatemala;

Search for other papers by Eduardo Arathoon in
Current site
Google Scholar
PubMed
Close
Restricted access

Histoplasmosis is one of the most common and deadly opportunistic infections among persons living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome in Latin America, but due to limited diagnostic capacity in this region, few data on the burden and clinical characteristics of this disease exist. Between 2005 and 2009, we enrolled patients ≥ 18 years of age with suspected histoplasmosis at a hospital-based HIV clinic in Guatemala City. A case of suspected histoplasmosis was defined as a person presenting with at least three of five clinical or radiologic criteria. A confirmed case of histoplasmosis was defined as a person with a positive culture or urine antigen test for Histoplasma capsulatum. Demographic and clinical data were also collected and analyzed. Of 263 enrolled as suspected cases of histoplasmosis, 101 (38.4%) were confirmed cases. Median time to diagnosis was 15 days after presentation (interquartile range [IQR] = 5–23). Crude overall mortality was 43.6%; median survival time was 19 days (IQR = 4–69). Mycobacterial infection was diagnosed in 70 (26.6%) cases; 26 (25.7%) histoplasmosis cases were coinfected with mycobacteria. High mortality and short survival time after initial symptoms were observed in patients with histoplasmosis. Mycobacterial coinfection diagnoses were frequent, highlighting the importance of pursuing diagnoses for both diseases.

Author Notes

Address correspondence to Blanca Samayoa, Asociación de Salud Integral, 2 av. 11-53 Zona 1, Guatemala City, Guatemala. E-mail: investigacion@asi.org.gt

Authors' addresses: Blanca Samayoa, Research and Development, Asociación de Salud Integral, Guatemala, Guatemala, and Facultad de Ciencias Químicas y Farmacia, Universidad de San Carlos de Guatemala, Guatemala, Guatemala, E-mail: investigacion@asi.org.gt. Monika Roy, Angela Ahlquist Cleveland, Christina M. Scheel, and Tom Chiller, Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: scmonika@gmail.com, ara0@cdc.gov, zsr3@cdc.gov, and tnc3@cdc.gov. Narda Medina, Dalia Lau-Bonilla, and Eduardo Arathoon, Research and Development, Asociación de Salud Integral, Guatemala, E-mails: nardagab@gmail.com, laubonilladml@yahoo.com, and earathoon@hotmail.com. Beatriz L. Gomez, School of Medicine and Health Sciences, Universidad del Rosario, Bogota, Colombia, and Corporación para Investigaciones Biológicas, Medellín, Colombia, E-mail: beatrizlgomez@hotmail.com.

  • 1.

    Colombo AL, Tobon A, Restrepo A, Queiroz-Telles F, Nucci M, 2011. Epidemiology of endemic systemic fungal infections in Latin America. Med Mycol 49 :785798.

  • 2.

    Marques SA, Robles AM, Tortorano AM, Tuculet MA, Negroni R, Mendes RP, 2000. Mycoses associated with AIDS in the Third World. Med Mycol 38 (Suppl 1): 269279.

  • 3.

    Couppie P, Aznar C, Carme B, Nacher M, 2006. American histoplasmosis in developing countries with a special focus on patients with HIV: diagnosis, treatment, and prognosis. Curr Opin Infect Dis 19: 443449.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Gómez B, 2011. Histoplasmosis: epidemiology in Latin America. Curr Fungal Infect Rep 5: 199205.

  • 5.

    Iriart X, Blanchet D, Menard S, Lavergne RA, Chauvin P, Adenis A, Cassaing S, Fillaux J, Magnaval JF, Demar M, Carme B, Bessieres MH, Couppie P, Nacher M, Berry A, Aznar C, 2014. A complementary tool for management of disseminated Histoplasma capsulatum var. capsulatum infections in AIDS patients. Int J Med Microbiol 304: 10621065.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Kauffman CA, 2009. Histoplasmosis. Clin Chest Med 30: 217225 v.

  • 7.

    Baddley JW, Sankara IR, Rodriquez JM, Pappas PG, Many WJ Jr, 2008. Histoplasmosis in HIV-infected patients in a southern regional medical center: poor prognosis in the era of highly active antiretroviral therapy. Diagn Microbiol Infect Dis 62: 151156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Caceres DH, Tobón AM, Cleveland AA, Scheel CM, Berbesi DY, Ochoa J, Restrepo A, Brandt ME, Chiller T, Gómez BL, 2016. Clinical and laboratory profile of persons living with human immunodeficiency virus/acquired immune deficiency syndrome and histoplasmosis from a Colombian hospital. Am J Trop Med Hyg 95: 918924.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Smith JA, Riddell J, Kauffman CA, 2013. Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep 15: 440449.

  • 10.

    Taylor RL, Dobrovolny CG, 1960. The distribution of histoplasmin sensitivity in Guatemala. Am J Trop Med Hyg 9: 518522.

  • 11.

    Segura L, Rojas M, Pelaez N, Shor-Posner G, RosaRe D, Moreno J, Klaskala W, Baum MK, 1997. Disseminated histoplasmosis and human immunodeficiency virus type 1 infection: risk factors in Guatemala. Clin Infect Dis 25: 343344.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Taylor ML, Chavez-Tapia CB, Vargas-Yanez R, Rodriguez-Arellanes G, Pena-Sandoval GR, Toriello C, Perez A, Reyes-Montes MR, 1999. Environmental conditions favoring bat infection with Histoplasma capsulatum in Mexican shelters. Am J Trop Med Hyg 61: 914919.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Scheel CM, Samayoa B, Herrera A, Lindsley MD, Benjamin L, Reed Y, Hart J, Lima S, Rivera BE, Raxcaco G, Chiller T, Arathoon E, Gomez BL, 2009. Development and evaluation of an enzyme-linked immunosorbent assay to detect Histoplasma capsulatum antigenuria in immunocompromised patients. Clin Vaccine Immunol 16: 852858.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Caceres DH, Scheel CM, Tobon AM, Ahlquist Cleveland A, Restrepo A, Brandt ME, Chiller T, Gomez BL, 2014. Validation of an enzyme-linked immunosorbent assay that detects Histoplasma capsulatum antigenuria in Colombian patients with AIDS for diagnosis and follow-up during therapy. Clin Vaccine Immunol 21: 13641368.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Agudelo CA, Restrepo CA, Molina DA, Tobon AM, Kauffman CA, Murillo C, Restrepo A, 2012. Tuberculosis and histoplasmosis co-infection in AIDS patients. Am J Trop Med Hyg 87: 10941098.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Djoba Siawaya JF, Ruhwald M, Eugen-Olsen J, Walzl G, 2007. Correlates for disease progression and prognosis during concurrent HIV/TB infection. Int J Infect Dis 11: 289299.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A, 2011. Immunological biomarkers of tuberculosis. Nat Rev Immunol 11: 343354.

  • 18.

    Allendoerfer R, Deepe GS Jr, 1998. Blockade of endogenous TNF-alpha exacerbates primary and secondary pulmonary histoplasmosis by differential mechanisms. J Immunol 160: 60726082.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Jaruratanasirikul S, Sriwiriyajan S, 1998. Effect of rifampicin on the pharmacokinetics of itraconazole in normal volunteers and AIDS patients. Eur J Clin Pharmacol 54: 155158.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20.

    Baciewicz AM, Chrisman CR, Finch CK, Self TH, 2013. Update on rifampin, rifabutin, and rifapentine drug interactions. Curr Med Res Opin 29: 112.

  • 21.

    Tucker R, Denning D, Hanson L, Rinaldi M, Graybill J, Sharkey P, Pappagianis D, Stevens D, 1992. Interaction of azoles with rifampin, phenytoin, and carbamazepine: in vitro and clinical observations. Clin Infect Dis 14: 165174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Stass H, Nagelschmitz J, Moeller JG, Delesen H, 2004. Pharmacokinetics of moxifloxacin are not influenced by a 7-day pretreatment with 200 mg oral itraconazole given once a day in healthy subjects. Int J Clin Pharmacol Ther 42: 2329.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Tobón AM, Franco L, Espinal D, Gómez I, Arango M, Trujillo H, Restrepo A, 1996. Disseminated histoplasmosis in children: the role of itraconazole therapy. Pediatr Infect Dis J 15: 10021008.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Huber F, Nacher M, Aznar C, Pierre-Demar M, El Guedj M, Vaz T, Vantilcke V, Mahamat A, Magnien C, Chauvet E, Carme B, Couppie P, 2008. AIDS-related Histoplasma capsulatum var. capsulatum infection: 25 years experience of French Guiana. AIDS 22: 10471053.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25.

    Tobon AM, Agudelo CA, Rosero DS, Ochoa JE, De Bedout C, Zuluaga A, Arango M, Cano LE, Sampedro J, Restrepo A, 2005. Disseminated histoplasmosis: a comparative study between patients with acquired immunodeficiency syndrome and non-human immunodeficiency virus-infected individuals. Am J Trop Med Hyg 73: 576582.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Kasuga T, White TJ, Koenig G, McEwen J, Restrepo A, Castaneda E, Da Silva Lacaz C, Heins-Vaccari EM, De Freitas RS, Zancope-Oliveira RM, Qin Z, Negroni R, Carter DA, Mikami Y, Tamura M, Taylor ML, Miller GF, Poonwan N, Taylor JW, 2003. Phylogeography of the fungal pathogen Histoplasma capsulatum. Mol Ecol 12: 33833401.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Karimi K, Wheat LJ, Connolly P, Cloud G, Hajjeh R, Wheat E, Alves K, Lacaz Cd Cda S, Keath E, 2002. Differences in histoplasmosis in patients with acquired immunodeficiency syndrome in the United States and Brazil. J Infect Dis 186: 16551660.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Durkin MM, Connolly PA, Karimi K, Wheat E, Schnizlein-Bick C, Allen SD, Alves K, Tewari RP, Keath E, 2004. Pathogenic differences between North American and Latin American strains of Histoplasma capsulatum var. capsulatum in experimentally infected mice. J Clin Microbiol 42: 43704373.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29.

    Goldani LZ, Aquino VR, Lunardi LW, Cunha VS, Santos RP, 2009. Two specific strains of Histoplasma capsulatum causing mucocutaneous manifestations of histoplasmosis: preliminary analysis of a frequent manifestation of histoplasmosis in southern Brazil. Mycopathologia 167: 181186.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Graviss EA, Vanden Heuvel EA, Lacke CE, Spindel SA, White AC Jr, Hamill RJ, 2000. Clinical prediction model for differentiation of disseminated Histoplasma capsulatum and Mycobacterium avium complex infections in febrile patients with AIDS. J Acquir Immune Defic Syndr 24: 3036.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Butt AA, Michaels S, Greer D, Clark R, Kissinger P, Martin DH, 2002. Serum LDH level as a clue to the diagnosis of histoplasmosis. AIDS Read 12: 317321.

  • 32.

    Couppie P, Sobesky M, Aznar C, Bichat S, Clyti E, Bissuel F, El Guedj M, Alvarez F, Demar M, Louvel D, Pradinaud R, Carme B, 2004. Histoplasmosis and acquired immunodeficiency syndrome: a study of prognostic factors. Clin Infect Dis 38: 134138.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Pietrobon D, Negro-Marquínez L, Kilstein J, Galíndez J, Greca A, Battagliotti C, 2004. Disseminated histoplasmosis and AIDS in an Argentine hospital: clinical manifestations, diagnosis and treatment. Enferm Infecc Microbiol Clin 22: 156159.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Putot A, Perrin S, Jolivet A, Vantilcke V, 2015. HIV-associated disseminated histoplasmosis in western French Guiana, 2002–2012. Mycoses 58: 160166.

  • 35.

    Wheat LJ, Hackett E, Durkin M, Connolly P, Petraitiene R, Walsh TJ, Knox K, Hage C, 2007. Histoplasmosis-associated cross-reactivity in the BioRad Platelia Aspergillus enzyme immunoassay. Clin Vaccine Immunol 14: 638640.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Hajjeh RA, Pappas PG, Henderson H, Lancaster D, Bamberger DM, Skahan KJ, Phelan MA, Cloud G, Holloway M, Kauffman CA, Wheat LJ, 2001. Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons. Clin Infect Dis 32: 12151220.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Myint T, Al-Hasan MN, Ribes JA, Murphy BS, Greenberg RN, 2014. Temporal trends, clinical characteristics, and outcomes of histoplasmosis in a tertiary care center in Kentucky, 2000 to 2009. J Int Assoc Provid AIDS Care 13: 100105.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Anderson AM, Mehta AK, Wang YF, Jing Q, Easley K, Nguyen ML, 2010. HIV-associated histoplasmosis in a nonendemic area of the United States during the HAART era: role of migration from endemic areas and lack of antiretroviral therapy. J Int Assoc Physicians AIDS Care (Chic) 9: 296300.

    • PubMed
    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 858 637 101
Full Text Views 632 19 0
PDF Downloads 278 17 0
 
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save