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 by GAFFI - The Global Action Fund for Fungal Infections. With more than 80,000 AIDS deaths worldwide attributed to histoplasmosis GAFFI have sent out an open letter to every pan American health organisation requesting that the deadly fungal disease is adopted as a priority by key public health agencies.
GAFFI’s President, David Denning who is Professor of Infectious Diseases in Global Health at The University of Manchester and 38 signatories from 13 countries want greater awareness of this deadly disease and more reliable and practical tests made available now, in those countries most affected.
A rough estimate of disseminated histoplasmosis in AIDS is 100,000 cases worldwide and 80,000 deaths 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 and described it 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 than or at least equivalent to the burden of HIV-tuberculosis and 100 times more than malaria (view article).
Disseminated histoplasmosis in AIDS is well recognised in the USA where awareness, laboratory capacities and access to effective antifungal therapy are all fully developed. But in Central and South America, and in Africa and SE Asia, it is usually undiagnosed or misdiagnosed as tuberculosis. 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 (at 10-21 days). The unavailability of even culture and microscopy in many countries, contributes to difficulties in identification of cases and prompt treatment initiation. A briefing document is here.
Professor Denning signed the letter on behalf of 38 key Physicians, Consultants, Health Directors, Infectious Disease Specialists and Mycologists globally.
Pneumocystis pneumonia - colonisation versus infection in both HIV positive and negative patients
Pneumocystis pneumonia (PCP) caused by P. jirovecii is a serious opportunistic infection frequently seen in HIV positive patients. Despite highly active antiretroviral therapy (HAART), it is still a serious life threatening opportunistic infection. Quantitative PCR on respiratory samples is the most sensitive and specific laboratory test, but the actual cut-off to define a case has been a matter for debate.
In a recently published retrospective study to examine qPCR cut-offs (Louis et al 2015) PCP was identified in BAL fluids in 56 HIV-positive and in 49 HIV-negative patients indicating that PCP is a significant occurrence in immunocompromised groups other than HIV. The direct fluorescence assay regarded as the gold standard for PCP diagnosis, showed a 92.8% sensitivity in HIV positive patients but only a 55.1% sensitivity in HIV negative patients; a lower fungal burden is seen in HIV negative patients.
A single cut-off at 1.5x104 copies/ml allowed the differentiation between colonized and infected HIV-positive patients with 100% sensitivity and specificity. In HIV-negative patients, cut-off values of 2.9x104 and 3.4x103 copies/ml resulted in 100% specificity and sensitivity, respectively.
Asymptomatic colonisation represents a real drawback to PCP diagnosis, especially using PCR.
Concordance between four real time PCR assays is discussed (Sasso et al. 2016). The genome of P. jiroveciii has recently been sequenced and its ability to survive in lungs better understood. Article.
Resistance detection straight from the blood culture bottle
Bloodstream Candida infections have a high mortality, and swift and appropriate treatment is vital as delays of just hours may significantly increase mortality.
In many countries, including Pakistan, C. tropicalis is the most predominant species, with a notable rise of frequency more recently. Also, growing resistance to fluconazole has become a serious concern and rapid antifungal susceptibility testing is necessary.
Jabeen and colleagues (2015) compared the gold standard conventional disk diffusion susceptibility test, with direct disk diffusion testing from positive blood bottles for fluconazole, voriconazole and amphotericin B. Excellent agreement was found between the conventional method and the direct disk diffusion method for all the azole drugs, but disk diffusion (both direct and conventional) was not an acceptable method for amphotericin B susceptibility testing (E-test MICs did not correlate with zone diameter).
The present study confirms that the disk method on direct blood culture bottles as a rapid and cost effective method of resistance detection.
Randomised study of adjunctive dexamethasone in cryptococcal meningitis shows worse outcomes:
A study of 451 patients form Vietnam, Laos, Indonesia, Uganda and Malawi who received adjunctive dexamethasome with either amphotericin B or fluconazole led to more disability, more adverse events and a slower clearance of C. neoformans from the CSF, writes Justin Beardsley in the New England Journal of Medicine. It was hypothesised that dexamethasone would improve outcomes which was NOT the case and the study was halted early because of the worse outcomes and adverse effects in the dexamethasone arm of the trial.
The authors concluded "With no effective adjunctive therapy yet identified, improving access to the most effective antifungal treatments, including flucytosine, must remain a global priority.”
More information; Link to article
Use twitter to see our weekly news items: Follow @LIFEworldwide