Epidemiology of Cryptococcus and cryptococcosis in Western Africa

Akaihe, Chidinma Lynda; Nweze, Emeka Innocent

doi:10.1111/myc.13188

Cited by 15 publications

(4 citation statements)

References 79 publications

(180 reference statements)

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“…The schematization of the most relevant clinical variables in COVID-19 cases associated with cryptococcosis is organized in Chart 1. Cryptococcus infections have high rates of morbidity and mortality, particularly in the context of immune suppression and when the central nervous system is compromised (GODINHO et al, 2017;AKAIHE & NWEZE, 2021;TORRE et al, 2022;RATHORE et al, 2022). At the same time, Motoa et al (2021) state that the proportion of HIV-uninfected patients who develop cryptococcosis has increased in recent years and propose that non-compliance with conditions such as severe comorbidities, advanced age, drug immunosuppression, and clinical inexperience may contribute to the delay in the diagnosis and treatment of cryptococcosis.…”

Section: Resultsmentioning

confidence: 99%

Secondary infection by Cryptococcus spp. in HIV-negative patients in the context of Covid-19

Norberg,

Manhães

et al. 2023

Interdisciplinarity and Innovation in Scientific Research

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Cryptococcosis is an infectious disease with worldwide distribution caused by fungi of the genus Cryptococcus, especially by the species C. neoformans and C. gattii. Cryptococcus infections begin with the inhalation of fungal particles that reach the lungs and can spread through hematogenous, especially in hosts with deficiencies in the cellular immune system. The acute respiratory syndrome in COVID-19 promotes a decrease in the efficiency of the immune system, either due to exhaustion resulting from the exacerbated response or due to immunosuppression in treatment with corticosteroids to contain the cytokine cascade in COVID-19, facilitating the appearance of opportunistic fungal infections in patients who develop severe cases of the virus due to SARS-CoV-2. The objective of this research is to conduct a review of clinical cases of cryptococcosis in co-infection with SARS-CoV-2 or the appearance of this mycosis in the post-COVID-19 convalescence period in HIV-uninfected individuals, analyzing the risk factors and circumstances associated with the relationship between cryptococcosis and COVID-19. Although cryptococcosis is a relatively rare infection among patients with COVID-19 and in the convalescence period of the disease, this opportunistic mycosis may be responsible for a mortality rate that is considered high (greater than 55%). Susceptibility to Cryptococcus spp. infection in the context of COVID-19 disease and treatment is strongly associated with corticosteroid use and pre-existing multiple comorbidities. It is not possible to determine the degree to which cryptococcosis is responsible for mortality in co-infection or infection during the COVID-19 convalescence period. The development of secondary infection by Cryptococcus spp. is indicative of a poor prognosis for the patient.

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Section: Resultsmentioning

confidence: 99%

Secondary infection by Cryptococcus spp. in HIV-negative patients in the context of Covid-19

Norberg,

Manhães

et al. 2023

Interdisciplinarity and Innovation in Scientific Research

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“…Even at that, there is a geographical disparity in data with the literature on CM in West Africa being sparse relative to East and Southern Africa. 65 Additionally, there are limited incidence cohort data on histoplasmosis despite the burden of HIV disease in sub-Saharan Africa, published studies on CPA are limited to two landmark papers and no data exist on the prevalence of IPA. 3 , 4 , 66 The scarcity of published research further compounds the knowledge gap contributing to low awareness.…”

Section: Blueprint For Ifi Pocts Availability In Africamentioning

confidence: 99%

Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa

Osaigbovo

Bongomin

2021

Therapeutic Advances in Infection

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Invasive fungal infections (IFIs) such as cryptococcosis, disseminated histoplasmosis, and chronic pulmonary aspergillosis are significant causes of morbidity and mortality in Africa. Lack of laboratory infrastructure and laboratory personnel trained in diagnostic mycology hamper prompt detection and management of IFIs on the continent. Point-of-care tests (POCT) obviate the need for complex infrastructure, skilled technicians, and stable electricity and have had major impacts on the diagnosis of bacterial, viral, and parasitic infections in low- and middle-income countries. Over the last 10 years, POCTs for IFIs have become increasingly available and they have the potential to revolutionize the management of these infections if scaled up in Africa. At the beginning of 2021, the World Health Organization (WHO) Essential Diagnostic List (EDL) included a cryptococcal antigen test for the diagnosis of cryptococcosis, Histoplasma antigen test for the diagnosis of disseminated histoplasmosis, and Aspergillus-specific test for the diagnosis of chronic pulmonary aspergillosis. All of these are available in formats that may be used as POCTs and it is hoped that this will improve the diagnosis of these life-threatening IFIs, especially in low- and middle-income countries. This perspective review discusses commercially available POCTs and outlines strategies of a blueprint to achieve their roll-out in Africa. The strategies include raising awareness, conducting research that uncovers the exact burden of IFIs, increasing advocacy, integrating diagnosis of IFIs into existing public health programs, adoption of the WHO EDL at country levels, and improving logistics and supply chains.

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“…Nonetheless, the mechanisms of fungal central nervous system (CNS) invasion have not been determined, which is also a mystery in cryptococcosis, a life-threatening fungal invasive disease, initialized by human pathogen Cryptococcus neoformans [17][18][19][20]. Cryptococcal diseases are predominant prevalent among immune compromised patients, such as HIV/AIDS, organ transplanted, systemic lupus erythematosus, and other immune associated diseases, and contribute about 15% of deaths in HIV/AIDS patients [21][22][23]. Seriously, morbidity of cryptococcosis in immune competent is increasing rapidly in China, Australia, Canada, and other countries and regions [24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…Cryptococcal meningoencephalitis are predominant prevalent among immune compromised patients, especially HIV/AIDS patients [18][19][20]. Mechanisms from clinical HIV/AIDS patients were the most direct approach to cryptococcus meningoencephalitis.…”

Section: Introductionmentioning

confidence: 99%

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain

Li¹,

Han²,

et al. 2022

Preprint

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Cryptococcal meningitis is a major risk for immune compromised patients mainly caused by the human opportunistic pathogen Cryptococcus neoformans, yet mechanisms of the brain or CNS dissemination remain to elucidate, which is the deadest process for the disease. Meanwhile, illustrations of clinically relevant responses in cryptococcosis were limited, as the low availabilities of clinical samples. In this study, macaque and mouse infection models were employed and miRNA-mRNA transcriptomes were performed and combined, which revealed cytoskeleton was a centric pathway regulated in both two organisms. Notably, myocilin, a novel modulator encoded by MYOC, was identified during cryptococcal pneumonia. An enhanced fungal burden was achieved in the brains of MYOC transgenic mice. Importantly, C. neoformans dissemination to the brain was inhibited by cytoskeleton inhibitor, which ruined “Trojan Horse” by dampening migration and phagocytosis of macrophages, but toxic to hosts. Taking together, this study provides new pathways and modulators during C. neoformans infections and reveals fundamental roles of cytoskeleton and MYOC in blocking fungal CNS dissemination that facilitate the development of novel drug targets for therapies of meningoencephalitis caused by C. neoformans and other pathogenic microorganisms.Author summaryFungal CNS dissemination is vital and lethal, which is the most important step for both fungal pathogenesis and host defense. Many milestones have been made to illustrate processes of invasion, such as the “Trojan Horse” derived by macrophages. However, blocking this “road” is still on the way. In our work, to mimic real responses in humans, macaque and mouse were included, miRNA-Seq and mRNA-Seq were combined, and we identified the core-pathway (cytoskeleton) during C. neoformans pathogenesis, which plays important roles in migration and phagocytosis for macrophages, key factors for macrophage “Trojan horse”, and cytoskeleton was also ruined in HIV/AIDS patients. Fungal brain dissemination was weakened by cytoskeleton inhibitor in mice. Meanwhile, we identified a novel modulator for macrophage “Trojan Horse”, MYOC, involved with C. neoformans brain dissemination. Consistently, we assume macrophages are the key executor cells for fungal CNS dissemination, and we propose the processes can be shut down by cytoskeleton or MYOC inhibitors. Our research would not only help to understand the high prevalence of cryptococcal meningitis in HIV/AIDS but also provides putative ways to block fungal cells invading the brain.

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Epidemiology of Cryptococcus and cryptococcosis in Western Africa

Cited by 15 publications

References 79 publications

Secondary infection by Cryptococcus spp. in HIV-negative patients in the context of Covid-19

Secondary infection by Cryptococcus spp. in HIV-negative patients in the context of Covid-19

Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa

Comparative miRNA Transcriptomics of Mouse and Macaque Reveals MYOC is An Inhibitor for C. neoformans Invasion into Brain

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