Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

Parkes-Ratanshi, Rosalind; Achan, Beatrice; Kwizera, Richard; Kambugu, Andrew; Meya, David B.; Denning, David W.

doi:10.1111/myc.12387

Cited by 43 publications

(46 citation statements)

References 69 publications

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“…ecent data from Uganda and Tanzania indicate that there are over 10,000 cases of HIV-related cryptococcosis per year in these countries alone (1,2). Of those, roughly 5,000 to 8,000 (54 to 79%) are fatal.…”

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confidence: 99%

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

et al. 2016

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Cryptococcal meningoencephalitis is a fungal infection that predominantly affects immunocompromised patients and is uniformly fatal if left untreated. Timely diagnosis is difficult, and screening or prophylactic measures have generally not been successful. Thus, we need a better understanding of early, asymptomatic pathogenesis. Inhaled cryptococci must survive the host immune response, escape the lung, and persist within the bloodstream in order to reach and invade the brain. Here we took advantage of the zebrafish larval infection model to assess the process of cryptococcal infection and disease development sequentially in a single host. Using yeast or spores as infecting particles, we discovered that both cell types survived and replicated intracellularly and that both ultimately established a sustained, low-level fungemia. We propose that the establishment and maintenance of this sustained fungemia is an important stage of disease progression that has been difficult to study in other model systems. Our data suggest that sustained fungemia resulted from a pattern of repeated escape from, and reuptake by, macrophages, but endothelial cells were also seen to play a role as a niche for cryptococcal survival. Circulating yeast collected preferentially in the brain vasculature and eventually invaded the central nervous system (CNS). As suggested previously in a mouse model, we show here that neutrophils can play a valuable role in limiting the sustained fungemia, which can lead to meningoencephalitis. This early stage of pathogenesis-a balanced interaction between cryptococcal cells, macrophages, endothelial cells, and neutrophils-could represent a window for timely detection and intervention strategies for cryptococcal meningoencephalitis. R ecent data from Uganda and Tanzania indicate that there are over 10,000 cases of HIV-related cryptococcosis per year in these countries alone (1, 2). Of those, roughly 5,000 to 8,000 (54 to 79%) are fatal. At a global scale, the survival rate is similarly poor, and over 600,000 deaths are attributed to Cryptococcus neoformans every year (3). The high mortality rate is in part due to difficulties in timely diagnosis; even in susceptible hosts, clinical signs of the initial pulmonary infection can be subtle or essentially absent (4). Studies in this population using serum cryptococcal antigen testing suggest that antigenemia (which may or may not represent actual fungemia) is a harbinger of meningoencephalitis but can precede it by weeks or more (5, 6). Once the infection has progressed to clinical meningoencephalitis, the prognosis is grim even with aggressive treatment. Beyond the HIV-infected population, a growing transplant and otherwise immunosuppressed population is also vulnerable, and even an immunocompetent host may be susceptible to infection and disease caused by the closely related species Cryptococcus gattii (7). An understanding of the events prior to fulminant disease is critical to better management of patients at risk for cryptococcal meningoencephalitis.While ...

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confidence: 99%

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

et al. 2016

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“…In addition, there is insufficient knowledge on the prevention, diagnosis, and treatment of serious fungal infections amongst health workers [5]. Fungal infections are common in Uganda [6]. It is estimated that about 2.5 million (6.5%) Ugandans suffer from at least one or more fungal infections every year [6].…”

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confidence: 99%

“…Fungal infections are common in Uganda [6]. It is estimated that about 2.5 million (6.5%) Ugandans suffer from at least one or more fungal infections every year [6]. People living with HIV are particularly at risk of opportunistic fungal infections.…”

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confidence: 99%

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Online Learning Resources Enhanced Teaching and Learning of Medical Mycology among Medical Students in Gulu University, Uganda

Bongomin

Erima

Kwizera

et al. 2020

Education Research International

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Background. The burden of serious fungal diseases has significantly increased in the past few decades; however, the number of health-care workers with expertise in the management of fungal diseases remains low, especially in low- and middle-income countries (LMICs). This study aimed to evaluate the use of freely available online teaching material to enhance teaching and learning of medical mycology among medical students in Gulu University Medical School, Uganda. Methods. We conducted a cross-sectional study among second year medical students undertaking Medical Mycology course on antifungal agents in the department of Medical Microbiology and Immunology in the academic year 2017-2018. The materials were synthesized and peer-reviewed by experts in fungal diseases and were made freely available on the Leading International Fungal Education website (http://www.LIFE-Worldwide.org). A local faculty in the department delivered the lectures, and pre- and posttest scores were evaluated statistically. Results. Sixty medical students participated in the study of which 78% were male. The average score was 41% for the pretest and 52% for the posttest (p<0.0001). There was no significant difference in the scores of males and females. Majority of the students gave an above-average rating for the course material; however, 54% preferred prerecorded videos. Conclusion. Using freely available online materials on medical mycology can enhance teaching and learning of medical mycology. Because of this, there is need to incorporate up-to-date information about the subject into the curriculums of medical schools especially in LMICs.

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“…Similar attempts have been made to estimate the burden of fungal disease for other countries in sub-Saharan Africa [98][99][100][101] and elsewhere. [4] Compared with other countries, SA has high burdens of HIV-associated and TB-associated fungal infections, reflecting the disproportionate size of these dual public health scourges.…”

Section: Researchmentioning

confidence: 99%

The estimated burden of fungal disease in South Africa

et al. 2019

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Fungal infections are common and diverse in South Africa (SA), driven in large part by the syndemics of HIV, tuberculosis (TB) and poverty. SA has the dubious distinctions of having the largest HIV epidemic, [1] one of the highest incidences of TB, [2] and-by some measures-the most socioeconomic inequity [3] in the world. Each of these conditions on its own or in combination can predispose individuals to fungal disease, but to our knowledge, the burden of such infections in SA has not previously been estimated. Objectives To estimate the prevalence and incidence of fungal infections in SA, excluding cutaneous infections with the sole exception of tinea capitis because of its severity in a significant minority of children. Methods The burden of fungal disease in SA was estimated using the methodologies of LIFE-worldwide.org. [4] Starting estimates for fungal disease or for conditions complicated by fungal disease were obtained This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

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Cryptococcal disease and the burden of other fungal diseases in Uganda; Where are the knowledge gaps and how can we fill them?

Cited by 43 publications

References 69 publications

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

A Zebrafish Model of Cryptococcal Infection Reveals Roles for Macrophages, Endothelial Cells, and Neutrophils in the Establishment and Control of Sustained Fungemia

Online Learning Resources Enhanced Teaching and Learning of Medical Mycology among Medical Students in Gulu University, Uganda

The estimated burden of fungal disease in South Africa

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