Pan American Health Organization · 1st edition, 2020
Evidence-based recommendations for rapid diagnosis and antifungal treatment of disseminated histoplasmosis in people with advanced HIV disease.
- Issuer
- Pan American Health Organization
- Edition
- 1st edition, 2020
- Audience
- HIV programme managers, policy-makers, national treatment advisory boards, implementing partners, and health-care professionals providing care for people living with HIV
- Evidence
- GRADE-rated recommendations based on systematic reviews and meta-analyses of diagnostic accuracy and treatment efficacy
- Reviewed
- 19 Oct 2026 · GMJ
What this guideline says
GMJ summary
These PAHO/WHO guidelines provide evidence-based recommendations for diagnosing and managing disseminated histoplasmosis among people living with HIV, a major cause of AIDS-related mortality in endemic regions. Histoplasmosis is estimated to be responsible for 5–15% of AIDS-related deaths annually in the Americas and causes up to 15,600 new cases and 4,500 deaths each year among people living with HIV in this region.
The guidelines recommend antigen detection as the preferred diagnostic method (sensitivity 95%, specificity 97%) over traditional culture-based methods. For treatment, liposomal amphotericin B 3.0 mg/kg for two weeks is recommended as induction therapy for severe or moderately severe disease, followed by itraconazole 200 mg twice daily for 12 months as maintenance therapy. Antiretroviral therapy should be initiated as soon as possible, except when central nervous system involvement is present.
While initially developed for the Americas where the disease burden is concentrated, these recommendations apply globally and are particularly relevant for countries in Asia and Africa where histoplasmosis is increasingly recognized among people with advanced HIV disease. The guidelines emphasize a public health approach to scaling up diagnosis and treatment in resource-limited settings.
Key points
For clinicians — doses and thresholds as stated in the guideline
- Diagnose disseminated histoplasmosis by detecting circulating Histoplasma antigens (sensitivity 95%, specificity 97%), preferred over culture or histopathology
- For severe or moderately severe disease: liposomal amphotericin B 3.0 mg/kg intravenously for two weeks as induction therapy; where unavailable, use deoxycholate amphotericin B 0.7–1.0 mg/kg for two weeks
- For mild to moderate disease: itraconazole 200 mg three times daily for three days, then 200 mg twice daily
- Maintenance therapy: itraconazole 200 mg twice daily for 12 months; may consider shorter duration (at least six months) if clinically stable, receiving antiretroviral therapy, with suppressed viral load and CD4 >200 cells/mm³
- Initiate antiretroviral therapy as soon as possible after starting antifungal treatment, except when central nervous system involvement is suspected or proven
- For TB coinfection: treat both infections according to WHO TB guidelines; monitor for drug–drug interactions between rifampicin and itraconazole
- Monitor renal function during amphotericin B therapy; ensure fluid and electrolyte reposition to reduce nephrotoxicity risk
- Consider immune reconstitution inflammatory syndrome (occurs at about 0.74 cases per 1,000 person-years), typically 60 days after antiretroviral therapy initiation; continue antiretroviral therapy and ensure optimal antifungal therapy if it occurs
Recommended treatment regimens for disseminated histoplasmosis by disease severity
Table extracted from the guideline
| Disease severity | Induction therapy | Duration | Maintenance therapy | Duration |
|---|---|---|---|---|
| Severe or moderately severe | Liposomal amphotericin B 3.0 mg/kg IV | 2 weeks | Itraconazole 200 mg twice daily | 12 months |
| Severe or moderately severe (alternative) | Deoxycholate amphotericin B 0.7–1.0 mg/kg IV | 2 weeks | Itraconazole 200 mg twice daily | 12 months |
| Mild to moderate | Itraconazole 200 mg TID × 3 days, then 200 mg BID | Until stable | Itraconazole 200 mg twice daily | 12 months |
Source: Pan American Health Organization, Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV. Reproduced in summary form.
From the guideline
Verbatim
“Histoplasmosis is one of the most frequent opportunistic infections caused by fungal pathogens among people living with HIV in the Americas and may be responsible for 5–15% of AIDS-related deaths every year in this Region.”
Editor’s perspective
Why this matters for Georgia and the region
Prof. Giorgi Pkhakadze, MD, MPH, PhD
Editor-in-Chief, Georgian Medical Journal · Chair, Public Health Institute of Georgia · WHO consultant, health and migration
As Georgia continues to strengthen its HIV treatment programme, which achieved commendable antiretroviral therapy coverage, we must not overlook opportunistic infections in people presenting with advanced disease. While histoplasmosis has not been systematically documented in our region, these guidelines remind us that diagnostic capacity often precedes disease recognition—we may simply not be looking for it. The recommendation I would emphasize to Georgian clinicians is the need for a high index of suspicion in any person with advanced HIV disease (CD4 <200 cells/mm³) presenting with non-specific systemic symptoms, particularly those with travel history to endemic regions or immigrants from Latin America, Africa, or Asia. The practical implementation challenge for Georgia will be ensuring access to both diagnostic capacity—Histoplasma antigen testing is now on the WHO Model List of Essential In Vitro Diagnostics—and to liposomal amphotericin B, which remains expensive and not widely available in our region; this may require advocacy through regional procurement mechanisms such as those we have successfully used for hepatitis C medications.
ORCID 0000-0001-7609-4515 · Perspective written for the GMJ Guidelines Library, 19 Oct 2026
Applicability
Georgia and the South Caucasus
While Georgia and the South Caucasus are not traditionally considered endemic regions for histoplasmosis, these guidelines are relevant for several reasons. First, returning travellers and migrants from endemic areas (Latin America, parts of Africa and Asia) may present with disseminated histoplasmosis in Georgian healthcare settings. Second, as diagnostic capacity improves globally, previously unrecognized endemic foci may be identified. Third, Georgia’s HIV programme, which provides antiretroviral therapy through the national programme, needs protocols for managing opportunistic infections in people presenting with advanced HIV disease (CD4 <200 cells/mm³). The recommendation for antigen detection testing is particularly relevant as Georgia strengthens laboratory capacity for diagnosing opportunistic infections. National HIV guidelines should incorporate screening protocols for histoplasmosis in people with advanced HIV disease who have resided in or travelled to endemic areas, and ensure access to appropriate antifungal medications, particularly liposomal amphotericin B and itraconazole, potentially through regional procurement mechanisms.
Questions this guideline answers
Quick answers
What defines severe or moderately severe disseminated histoplasmosis?
Severe or moderately severe disease is defined as having at least one sign or symptom involving vital organs: respiratory or circulatory failure, neurological signs, renal failure, coagulation anomalies, or WHO performance status greater than 2 (confined to bed or chair more than half of waking hours with only limited self-care capability). All other presentations are classified as mild to moderate.
Can maintenance therapy be stopped before 12 months?
Yes, shorter courses (at least six months) may be considered when the person is clinically stable, receiving antiretroviral therapy, has suppressed viral load, and has immune recovery (CD4 >200 cells/mm³). This is a conditional recommendation based on very-low-certainty evidence, and the decision should be individualized.
How should TB and histoplasmosis coinfection be managed?
People with both TB and histoplasmosis should receive TB therapy according to WHO guidelines. However, rifampicin leads to subtherapeutic itraconazole levels, so clinicians should monitor itraconazole blood levels if possible, consider extending amphotericin B induction therapy, increasing itraconazole dose, or replacing rifampicin with rifabutin where feasible.
What monitoring is needed during amphotericin B treatment?
Renal function should be monitored to prevent nephrotoxicity. Provide appropriate fluid and electrolyte reposition and infuse deoxycholate amphotericin B over 4–6 hours. Monitor for infusion-related reactions, anemia, hypokalemia, and hypomagnesemia. Clinical response including fever, fatigue, and other symptoms should be assessed daily during initial induction therapy.
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- Issuer
- Pan American Health Organization
- Type
- Procedures, manuals, guidelines
- Edition
- 1st edition, 2020
- Status
- Current
- Published
- 2020-01-01
- Languages
- English, Spanish, Portuguese
- Scope
- Diagnosis, treatment, and management of disseminated histoplasmosis in people living with HIV globally, with initial focus on Latin America and the Caribbean
- Audience
- HIV programme managers, policy-makers, national treatment advisory boards, implementing partners, and health-care professionals providing care for people living with HIV
- Licence
- CC BY-NC-SA 3.0 IGO
- ISBN
- 978-92-75-12248-8
- Evidence
- GRADE-rated recommendations based on systematic reviews and meta-analyses of diagnostic accuracy and treatment efficacy
- Next review
- Not specified
- Record history
- Created 19 Oct 2026 · updated 19 Oct 2026 · next check Apr 2027
Pan American Health Organization, World Health Organization. Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV. Washington, D.C.: PAHO/WHO; 2020. (PAHO ISBN: 978-92-75-12248-8; WHO ISBN: 978-92-4-000644-7).GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.
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