Can histoplasmosis reactivate from a previous infection?

Histoplasmosis Reactivation from Previous Infection

Yes, histoplasmosis can reactivate from a previous infection, particularly in immunocompromised individuals such as those with HIV/AIDS, organ transplant recipients, or patients on immunosuppressive medications. 1

Pathophysiology of Reactivation

• Histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum, which can remain dormant in tissues after primary infection 1
• Reactivation occurs primarily when cellular immunity wanes, such as when CD4+ T-lymphocyte counts fall below 150 cells/μL in HIV-infected individuals 1
• During primary infection, dissemination from the lungs to other tissues likely occurs in all infected individuals during the first 2 weeks before specific immunity develops, but is usually controlled and becomes nonprogressive in immunocompetent hosts 1
• Latent foci of infection can persist for years before reactivating when immune function declines 2

Risk Factors for Reactivation

• CD4+ count <150 cells/μL in HIV-infected individuals is the most significant risk factor 1, 2
• History of previous exposure to Histoplasma capsulatum, especially in endemic areas (Ohio and Mississippi River Valleys, Latin America) 1, 2
• Positive baseline serology for complement-fixing antibodies to Histoplasma mycelium antigen 2
• Immunosuppression from organ transplantation, autoimmune disease treatments, or other causes 1
• Residence in or travel history to endemic regions, though reactivation can occur years after leaving these areas 1, 3

Clinical Manifestations of Reactivated Disease

• Disseminated histoplasmosis is the most common presentation of reactivated disease 1
• Prolonged fever is the most common presenting symptom in both adults and children 1
• Other common manifestations include:
  • Weight loss, fatigue, and hepatosplenomegaly 1
  • Respiratory symptoms (cough, chest pain, dyspnea) in approximately 50% of patients 1
  • CNS involvement with meningitis and focal brain lesions, particularly in severely immunocompromised patients 1
  • Cutaneous lesions that may be erythematous and nodular 1
  • Hematologic abnormalities including anemia and thrombocytopenia 1

Diagnosis of Reactivated Histoplasmosis

• Detection of Histoplasma antigen in urine (95% sensitivity) or serum (85% sensitivity) is the most rapid and sensitive diagnostic method for disseminated disease 1
• Blood cultures using lysis-centrifugation technique are positive in >85% of AIDS patients with disseminated histoplasmosis but may take up to 6 weeks to grow 1
• Histopathologic examination of tissue biopsies showing characteristic 2-4 μm budding yeast forms 1
• For CNS involvement, CSF should be tested for Histoplasma antigen, antibody, and culture, though CSF culture is only positive in 20-60% of cases 1

Treatment of Reactivated Disease

• For moderate to severe disseminated disease:

  • Initial therapy with liposomal amphotericin B for 3-10 days until clinical improvement occurs 1
  • Liposomal amphotericin B is more effective than standard deoxycholate formulation, with more rapid response, lower mortality, and reduced toxicity 1
  • After initial improvement, transition to oral itraconazole to complete 12 weeks of treatment 1

• For mild to moderate disease:

  • Itraconazole capsules for 12 weeks 1
  • Fluconazole 800 mg daily is an alternative if patients cannot tolerate itraconazole, but is less effective 1

• For CNS involvement:

  • Amphotericin B should be continued for 12-16 weeks, followed by maintenance therapy 1

Prevention of Recurrence

• Lifelong suppressive therapy (secondary prophylaxis) with itraconazole 200 mg twice daily is recommended for patients with severe disseminated or CNS infection and in patients who relapse despite appropriate therapy 1
• In HIV-infected patients who respond to antiretroviral therapy with sustained CD4+ counts >150 cells/μL, discontinuation of suppressive therapy may be considered 1
• Suppressive therapy should be resumed if the CD4+ count decreases to <150 cells/μL 1

Special Considerations

• Azole antifungals should be avoided during the first trimester of pregnancy due to teratogenicity risk 1
• Amphotericin B should be substituted for itraconazole or fluconazole during the first trimester of pregnancy 1
• Sporadic cases of histoplasmosis can be diagnosed outside endemic areas due to reactivation of previous infection, highlighting the importance of considering this diagnosis even in non-endemic regions 1, 3