Access to flucytosine for HIV-infected patients with cryptococcal meningitis - an urgent need

Govender, Nelesh P.; Meintjes, Graeme; Banoo, Shabir

doi:10.7196/samj.8713

Cited by 7 publications

(9 citation statements)

References 5 publications

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“…Perhaps foremost among the medications to which access is urgently needed is flucytosine, an over-50-year-old medicine shown to reduce mortality from cryptococcal meningitis compared with alternatives, but which remains inaccessible in SA. [103,104]…”

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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Section: Researchmentioning

confidence: 99%

The estimated burden of fungal disease in South Africa

et al. 2019

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“…In resource limited countries where 5-FC may be frequently unavailable, it is recommended that adults are started on a high-dose fluconazole regime with AMB if the latter is available [ 22 ]. However, Day et al published that AMB and fluconazole combination therapy did not increase patient survival in a Vietnamese cohort and called for greater access to 5-FC; a call echoed by others [ 24 , 25 , 26 , 27 ]. Infection relapse can also occur, particularly in patients who are not receiving maintenance therapy or antiretroviral therapy [ 28 ].…”

Section: Molecular Targets Of Antifungal Drugs and Drug Limitationmentioning

confidence: 99%

Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

Lev

Saiardi

et al. 2016

JoF

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Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP). We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P) and pyrophosphate (PP) groups covalently attached at different positions. This review focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans; (2) the identification of PP-IP5 (IP7) as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3) why IPK enzymes represent suitable candidates for drug development.

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“…197 Similarly, cryptococcal disease is also frequently treated with fluconazole despite clear evidence of flucytosine and amphotericin B being more effective. 198,199 Despite being added to the essential medicines list, national drug licensing issues and higher production costs may impede their use. 193 Similar issues affect the treatment of obstructive lung disease and malignancy.…”

Section: Availability Of Drugs and Monitoringmentioning

confidence: 99%

Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease

Rylance

Meghji

Miller

et al. 2016

Semin Respir Crit Care Med

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Respiratory tract infection, particularly tuberculosis, is a major cause of mortality among human immunodeficiency virus (HIV)-infected individuals. Antiretroviral therapy (ART) has resulted in a dramatic increase in survival, although coverage of HIV treatment remains low in many parts of the world. There is a concurrent growing burden of chronic noninfectious respiratory disease as a result of increased survival. Many risk factors associated with the development of respiratory disease, such as cigarette smoking and intravenous drug use, are overrepresented among people living with HIV. In addition, there is emerging evidence that HIV infection may directly cause or accelerate the course of chronic lung disease. This review summarizes the clinical spectrum and epidemiology of respiratory tract infections and noninfectious pulmonary pathologies, and factors that explain the global variation in HIV-associated respiratory disease. The potential for enhancing diagnoses of noninfective chronic conditions through the use of clinical algorithms is discussed. We also consider issues in assessment and management of HIV-related respiratory disease in view of the increasing global scale up of ART.

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Access to flucytosine for HIV-infected patients with cryptococcal meningitis - an urgent need

Cited by 7 publications

References 5 publications

The estimated burden of fungal disease in South Africa

The estimated burden of fungal disease in South Africa

Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

Global Considerations in Human Immunodeficiency Virus-Associated Respiratory Disease

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