(C) PLOS One [1]. This unaltered content originally appeared in journals.plosone.org.
Licensed under Creative Commons Attribution (CC BY) license.
url:https://journals.plos.org/plosone/s/licenses-and-copyright

------------



Histoplasmosis in Africa: Current perspectives, knowledge gaps, and research priorities

['Bright K. Ocansey', 'Division Of Infection', 'Immunity', 'Respiratory Medicine', 'Faculty Of Biology', 'Medicine', 'Health', 'University Of Manchester', 'Manchester Academic Health Science Centre', 'Manchester']

Date: 2022-04

X-ray findings indicating early bone involvement include reduction in the corticomedullary differentiation of the distal metaphysis, spiculated periosteal reaction, cortical erosion, multiple calcified and noncalcified soft tissue lesions, as well as multiple osteolytic lesions with a sclerotic rim [ 38 ]. In subcutaneous lesions, MRI may show lesions that are hyperintense on T2-weighted images and show peripheral rim enhancement. However, bone lesions appear hypointense on T1-weighted images, without rim enhancement after contrast administration.

Imaging studies are essential when lung or bones are involved and can also be used in monitoring therapy or identifying relapse [ 26 ]. X-rays, magnetic resonance imaging (MRI), and computed tomography (CT) have been documented to be useful and employed in Africa [ 11 , 14 , 8 , 38 ]. For cases involving the lung, the common radiographic findings are bilateral diffuse opacities, pulmonary infiltrates, nodules, pleural effusion, and nodular cavitation [ 9 , 18 ]. These findings are common in TB, and considering the high TB burden in Africa maybe a recipe for misdiagnosis. CT scan may be necessary to confirm uncertain X-ray findings or demonstrate uncommon features such as disseminated nodules [ 38 ].

Laboratory diagnosis.

Direct microscopy is the simplest, most common, and in majority of the cases, the only available method for the diagnosis of histoplasmosis in several African countries [89]. Smear preparation of exudate or purulent discharge are stained or unstained based on available resources. Used stains include Giemsa, lactophenol cotton blue (LPCB), and Gomori’s methenamine silver (GMS). The use of potassium hydroxide (KOH) also yields good results [24]. Yeast cells of particularly hcd are common in suppurative materials from skin lesions, abscess, discharging sinuses, and bone lesions. Unfortunately, direct microscopy may not confidently detect cases of histoplasmosis as the morphology of H. capsulatum is similar to other fungi.

The isolation of H. capsulatum from clinical samples is critical to confirm the diagnosis of histoplasmosis but not generally available or accessible in most laboratories in Africa. Culture is achieved on enriched media such as Sabouraud dextrose agar (SDA) and brain heart infusion (BHI) agar, but its growth is slow, sometimes taking up to 8 weeks. Although it is considered a Class 3 pathogen and requires the use of at least a Class II biosafety cabinet, there is no record of a laboratory-acquired case of histoplasmosis. Macroscopic and microscopic morphology of colonies at room temperature is similar for Hcc and Hcd. Inoculation of primary colonies in appropriate media converts mycelial forms to large yeast forms at 37°C [23]. Suitable media for the conversion include blood or BHI agar supplemented with cysteine or glutamine [23]. H. capsulatum is usually considered urease negative but may occasionally also be urease positive [7].

The histopathological picture is believed to be identical for classical and African histoplasmosis but may mimic other mycoses blastomycosis, cryptococcosis, and emergomycosis. It is the second common laboratory approach in detecting histoplasmosis in Africa. The histological examination reveals aggregates of multinucleate giant cells containing oval, double-contoured yeast cells. Yeast cells mostly show the “hourglass” or “figure 8” budding, and presence of bud scars is common. The size of the yeast cells is larger, and the walls are thicker in Hcd than in Hcc. The yeast cells may be isolated or sometimes occur in chains of 4 or 5 [35]. Like other fungal infections, staining with only hematoxylin–eosin (HE) may be unsatisfactory, and addition of special stains, periodic acid–Schiff (PAS), and GMS is recommended for better demonstration of yeast cells. Experience is needed to avoid confusing yeast cells of Hcd with other fungi such as capsule-deficient Cryptococcus spp. and small variants of Blastomyces spp. A positive reaction with mucicarmine is discriminatory for Cryptococcus spp.: Blastomyces spp. generally has single broad-based buds and is multinucleated on PAS and GMS stains.

The role of immunoassays is currently common in classical histoplasmosis but rarely utilized in Africa. Immunodiffusion and immunofluorescence tests are generally available and occasionally used, but lack consistency, and are often less useful, especially, in immunocompromised patients [42,52]. These assays are not discriminatory between Hcc and Hcd. Galactomannan (GM) and glucan with ß1 to ß4 linkages and ß1 to ß3 linkages are known cell wall and in the mycelial wall constituent of both Hcc and Hcd. The use of GM and beta-D-glucan (BDG) in the diagnosis of African histoplasmosis is unclear, as it has not been extensively used in comparison to classical histoplasmosis. In 2 cases of African histoplasmosis that had Aspergillus GM tested, one was positive and the other negative [9,37]. Although it has been suggested that the current commercial Histoplasma GM LFA and EIA also detect Hcd, there is currently no evaluation studies to that effect (personal communication).

Molecular identification of Hcc and Hcd are not commonly done in Africa except in few research or tertiary medical settings. Molecular analysis includes panfungal PCR or specific PCR and DNA sequencing of PCR products. These techniques are scarcely available. In a rare clinical experience, Hcd was rapidly detected with PCR and DNA sequencing within 24 hours of admission [36].

Generally, among the 110 cases from both case reports and series of locally diagnosed Hcd and Hcc reviewed, diagnosis was made by histopathology in 96 (87.3%) cases either alone or with direct microscopy, culture, or PCR. Direct microscopy was done in 34 (30.9%) cases and in 20 cases was the only form of diagnosis. Confirmatory diagnosis with culture was done in 22 (20.0%) cases, with positive results in 17, all by phenotypic analysis. Molecular identification was done in only 1 case, on a peripheral blood specimen. Confirmatory of histology diagnosis by PCR and immunohistochemistry was employed in 4 and 12 cases, respectively.

[END]

[1] Url: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0010111

(C) Plos One. "Accelerating the publication of peer-reviewed science."
Licensed under Creative Commons Attribution (CC BY 4.0)
URL: https://creativecommons.org/licenses/by/4.0/


via Magical.Fish Gopher News Feeds:
gopher://magical.fish/1/feeds/news/plosone/

You are viewing proxied material from magical.fish. The copyright of proxied material belongs to its original authors. Any comments or complaints in relation to proxied material should be directed to the original authors of the content concerned. Please see the disclaimer for more details.