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Global Action Fund for Fungal Infections calls for stakeholders to address histoplasmosis in AIDS

February 16 2016

A campaign to convince Latin American countries to do more to tackle a problem which is the leading cause of death in AIDS and yet is poorly understood, often misdiagnosed and frequently left untreated has been launched today.

Experts from GAFFI (Global Action Fund for Fungal Infections) believe more than 80,000 AIDS deaths worldwide can be attributed to histoplasmosis. They want the deadly fungal disease adopted as a priority by key public health agencies and have today sent out an open letter to every pan American health organisation.  
GAFFI’s President is Dr David Denning who is Professor of Infectious Diseases in Global Health at The University of Manchester. He wants greater awareness of the deadly disease and more reliable and practical tests made available in those countries most affected.

A recent rough estimate of disseminated histoplasmosis in AIDS is 100,000 cases worldwide and 80,000 deaths (view article) mostly due to lack of diagnosis and partly unavailability of treatment. If the UNAIDS target of reducing AIDS deaths to under 500,000 is to be achieved, action needs to be taken now on disseminated histoplasmosis. A group of institutions from the Americas recently declared HIV-associated histoplasmosis a neglected disease described as: "an invisible elephant out of the radar of International Health authorities, organizations and funders". They estimated that histoplasmosis was responsible for 1 in 5 AIDS-related deaths in the Americas, more or at least equivalent to the burden of HIV-tuberculosis and 100 times more than malaria.
Disseminated histoplasmosis in AIDS is well recognised in the USA where awareness, laboratory capacities and access to effective antifungal therapy are all fully developed. In Central and South America, and in Africa and SE Asia, it is usually undiagnosed or misdiagnosed as tuberculosis.

 View the Open Letter:   A few current examples: the median age of cases in Panama is 33 years, and 59% of these patient die. In Manaus, Brazil, the age range of cases is 12-42 years, with an overall mortality of 48%, and in the Northeast of this country, a burden of 208 cases of disseminated histoplasmosis in AIDS patients was detected in a period of 4 years, with 42% fatal.
Histoplasmosis is an airborne infection related primarily to bat and bird guano exposure in soil. There are particular ‘hot spots’ mostly identified in the Americas, but it is a worldwide pathogen, with cases described in most African countries, SE Asia, India and China. It is grossly under-diagnosed because of the low sensitivity (average 50%) of stained smears and the slow growth of organism in special medium culture (which is not available in many locations). In AIDS, the culture usually becomes positive after the patient has died (10-21 days). The unavailability of even culture and microscopy in many countries, contributes to difficulties in case identification and prompt treatment initiation. A briefing document is here.

A patient with histoplasmosis

Rapid diagnosis with antigen testing and PCR are excellent; results can be provided in under 24 hours. We profiled this in the ’95-95 by 2025’ Roadmap issued in May 2015 (page 5). An antigen testing kit is commercially available from IMMY, and they are field testing a point of care Histoplasma antigen test, which will take about an hour for diagnosis. Other companies are also working on this. PCR is not commercially available, but could be with the right purchase incentives, and is done routinely in Spain, Colombia, Argentina, Guatemala, and French Guiana. Treatment works well. Amphotericin B and itraconazole are the drugs of choice with 87-100% response rates in AIDS in the USA.
Itraconazole is widely available (see country distribution on the map). Low doses work for histoplasmosis.

For very ill patients, amphotericin B is preferable. Unfortunately this is not as widely available as it should be (see map ). Amphotericin B is also required for optimal treatment of cryptococcal meningitis, another common cause of death in AIDS. Histoplasmosis doesn’t only affect AIDS patients. It can affect people without underlying conditions and other immunocompromised patients, and the chronic cavitary form can mimic pulmonary TB (a cause of ‘smear negative TB’)

Numerous issues were identified at an international workshop on disseminated histoplasmosis in AIDS recently held in Suriname (www.gaffi.org/histoplasmosis-the-leading-aids-diagnosis-in-the-guiana-shield-and-parts-of-central-america/).

GAFFI's open letter outlines the morbidity and mortality burdens and demands action of all stakeholders to realize the following measures:

1. To enable direct, rapid access to reliable and practical diagnostic tests in all areas where histoplasmosis occurs or is suspected;
2. To define the real extend of morbidity and mortality of histoplasmosis so as to define all histoplasmosis endemic areas in the world;
3. To bring therapy for histoplasmosis within the reach of all who need it, especially in endemic areas
4. To stimulate scientific investigation on histoplasmosis epidemiology, diagnosis and treatment
5. To organize regular conferences and educational sessions concerning histoplasmosis with support for those living in endemic areas to participate and enable disease awareness amongst treating physicians.
Professor Denning signed the letter on behalf of 38 key  Physicians , Consultants , Health Directors, Infectious Disease Specialists and Mycologists globally.