IntroductionDisseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List.ObjectiveOur objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries.MethodsA systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. PubMed, Scopus, Lilacs and Scielo databases were searched for published articles between 1981 and 2018. There was no language restriction.ResultsOf 1327 screened abstracts we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneousgroup of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Six studies did not systematically use mycologically confirmed cases as a gold standard but compared antigen detection tests against another antigen detection test. Patient numbers were generally small (19–65) in individual studies and, in most (7/10), no confidence intervals were given. The post test probability of a positive or negative test were good suggesting that this non invasive diagnostic tool would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. The first results evaluating point of care antigen detection tests using a lateral flow assay were promising with high sensitivity and specificity.ConclusionsAntigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease.
Background: Histoplasmosis is a neglected acquired immune deficiency syndrome (AIDS)-defining disease in sub-Saharan African countries, which is commonly misdiagnosed as tuberculosis (TB) due to similar imagery and clinical features; patients usually receive presumptive anti-TB treatment that is considered as anti-TB treatment failure. Patients with advanced human immunodeficiency virus (HIV) disease (AHD), CD4<200/mm3 or World Health Organisation clinical stage 3 or 4, develop disseminated histoplasmosis (DH) diagnosed at a late stage or at post-mortem, owing to poor clinical suspicion, lack of rapid diagnosis tools to offer rapid and accurate results, and non-availability and accessibility of appropriate antifungal medications. We report 31 cases of DH amongst patients with AHD in sub-Saharan African population from the literature, highlighting the challenging care issue in sub-Saharan Africa. Results: Out of 31 reported cases 64.51% (20/31) were caused by Histoplasma capsulatum var capsulatum, 48.38% (15/31) being immigrants in Europe, Canada and Japan, with 41.93% (13/31) mortality, and 6 cases having no reported outcome. The poor index of suspicion on the part of clinicians; the lack of skilled laboratory personnel and rapid and accurate diagnosis tools of histoplasmosis for a proper detection of either classical or African histoplasmosis coexisting in many sub-Saharan African countries; and the non-availability and accessibility of appropriate antifungal medications were the most challenges in caring DH in advanced HIV disease population in sub-Saharan Africa. Conclusion: there is a need for prompt and routine screening of advanced HIV disease patients in sub-Saharan Africa for histoplasmosis as an AIDS-defining illness.
Histoplasmosis, tuberculosis and HIV are all highly prevalent in sub-Saharan Africa (SSA). Co-occurrence of two or more of these infections has been reported in several populations of patients, especially those with advanced HIV infection where these opportunistic infections contribute to a significant morbidity and mortality. With a high burden of pulmonary tuberculosis (PTB) secondary to HIV in SSA, histoplasmosis is commonly misdiagnosed as smear-negative PTB in HIV patients due to similar clinical and radiological presentations. This is also partly the result of the lack of trained clinical and laboratory personnel to make a definite diagnosis of histoplasmosis. There is a low index of clinical suspicion for histoplasmosis, and cases are mostly discovered accidently and documented through case reports and case series. Similarly, the high cost and lack of fungal diagnostics in most SSA countries makes it difficult to make a diagnosis. There is a need to build local capacity for mycology so that patients are managed to improve on the index of clinical suspicion and diagnostic capabilities. Moreover, simple accurate point-of-care diagnostic tests and first-line antifungal treatment for histoplasmosis are not available in many SSA countries. This review describes the existence of co-infections of histoplasmosis, tuberculosis and HIV in SSA, highlighting the challenges and research priorities.
Fungal infections are frequent in Cameroon, and invasive fungal infections are sometimes detected, usually in HIV-infected patients. For these reasons, we have estimated the burden of fungal infections. Using published literature and population estimates for the at-risk group, we used deterministic modelling to derive national incidence and prevalence estimates for the most serious fungal diseases. HIV infection is common and an estimated 120,000 have CD4 counts <200 × 106/mL and commonly present with opportunistic infection. Oesophageal candidiasis in HIV is common, and in poorly controlled diabetics. We estimate 6720 cases of cryptococcal meningitis, 9000 of Pneumocystis pneumonia, 1800 of disseminated histoplasmosis annually complicating AIDS, and 1200 deaths from invasive aspergillosis in AIDS, but there are no data. We found that 2.4% of adults have chronic obstructive pulmonary disease (COPD) and 2.65% have asthma, with “fungal asthma” affecting 20,000. Chronic pulmonary aspergillosis probably affects about 5000 people, predominantly after tuberculosis but also with COPD and other lung diseases. Also, tinea capitis in schoolchildren is frequent. Overall, an estimated 1,236,332 people are affected by a serious fungal infection. There is an urgent need for government and clinician attention, improved laboratory facilities, fungal diagnostic tests, and competent laboratory technicians, as well as all World Health Organization (WHO)-endorsed essential antifungal drugs to be made available, as only fluconazole is registered and available in the country.
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