Journal Article > ResearchFull Text
Int J Infect Dis. 1 June 2020; Volume 95; 459-461.; DOI:10.1016/j.ijid.2020.02.057
Shroufi A, Govender NP, Meintjes GA, Black JM, Nel J, et al.
Int J Infect Dis. 1 June 2020; Volume 95; 459-461.; DOI:10.1016/j.ijid.2020.02.057
BACKGROUND
Cryptococcal Meningitis (CM) is estimated to cause 181,000 deaths annually; with the majority occurring in Sub Saharan Africa. Flucytosine is recommended by the World Health Organization as part of the treatment for CM. Widespread use of flucytosine could reduce mortality in hospital by as much as 40% compared to the standard of care, yet due to market failure quality assured flucytosine remains unregistered and largely inaccessible throughout Africa.
METHODS
The recently established South African flucytosine clinical access programme is an attempt to address market failure which led to a lack of public-sector access to flucytosine for cryptococcal meningitis, by making the medicine freely available to tertiary hospitals in South Africa.
RESULTS
Between November 2018 and September 2019, 327 CM patients received flucytosine through this programme, with efforts to support sustainable national scale up presently ongoing. We describe why this programme was needed, its catalytic potential, what is still required to ensure widespread access to flucytosine, and observation from this experience that may have wider relevance.
CONCLUSIONS
The South African Flucytosine Access Programme illustrates how access programmes may be one part of the solution to addressing the vicious cycle of perceived low demand, limiting manufacturer interest in specific product markets.
Cryptococcal Meningitis (CM) is estimated to cause 181,000 deaths annually; with the majority occurring in Sub Saharan Africa. Flucytosine is recommended by the World Health Organization as part of the treatment for CM. Widespread use of flucytosine could reduce mortality in hospital by as much as 40% compared to the standard of care, yet due to market failure quality assured flucytosine remains unregistered and largely inaccessible throughout Africa.
METHODS
The recently established South African flucytosine clinical access programme is an attempt to address market failure which led to a lack of public-sector access to flucytosine for cryptococcal meningitis, by making the medicine freely available to tertiary hospitals in South Africa.
RESULTS
Between November 2018 and September 2019, 327 CM patients received flucytosine through this programme, with efforts to support sustainable national scale up presently ongoing. We describe why this programme was needed, its catalytic potential, what is still required to ensure widespread access to flucytosine, and observation from this experience that may have wider relevance.
CONCLUSIONS
The South African Flucytosine Access Programme illustrates how access programmes may be one part of the solution to addressing the vicious cycle of perceived low demand, limiting manufacturer interest in specific product markets.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 18 October 2018; Volume 19 (Issue 4); DOI:10.1016/S1473-3099(18)30493-6
Loyse A, Burry J, Cohn J, Ford NP, Chiller T, et al.
Lancet Infect Dis. 18 October 2018; Volume 19 (Issue 4); DOI:10.1016/S1473-3099(18)30493-6
In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 29 June 2017; Volume 11 (Issue 6); e0005575.; DOI:10.1371/journal.pntd.0005575
Molloy SF, Chiller T, Greene GS, Burry J, Govender NP, et al.
PLoS Negl Trop Dis. 29 June 2017; Volume 11 (Issue 6); e0005575.; DOI:10.1371/journal.pntd.0005575
Journal Article > ReviewAbstract
Lancet Infect Dis. 31 May 2013; Volume 13 (Issue 7); DOI:10.1016/S1473-3099(13)70078-1
Loyse A, Thangaraj H, Easterbrook PJ, Ford NP, Roy M, et al.
Lancet Infect Dis. 31 May 2013; Volume 13 (Issue 7); DOI:10.1016/S1473-3099(13)70078-1
Cryptococcal meningitis is the leading cause of adult meningitis in sub-Saharan Africa, and contributes up to 20% of AIDS-related mortality in low-income and middle-income countries every year. Antifungal treatment for cryptococcal meningitis relies on three old, off-patent antifungal drugs: amphotericin B deoxycholate, flucytosine, and fluconazole. Widely accepted treatment guidelines recommend amphotericin B and flucytosine as first-line induction treatment for cryptococcal meningitis. However, flucytosine is unavailable in Africa and most of Asia, and safe amphotericin B administration requires patient hospitalisation and careful laboratory monitoring to identify and treat common side-effects. Therefore, fluconazole monotherapy is widely used in low-income and middle-income countries for induction therapy, but treatment is associated with significantly increased rates of mortality. We review the antifungal drugs used to treat cryptococcal meningitis with respect to clinical effectiveness and access issues specific to low-income and middle-income countries. Each drug poses unique access challenges: amphotericin B through cost, toxic effects, and insufficiently coordinated distribution; flucytosine through cost and scarcity of registration; and fluconazole through challenges in maintenance of local stocks-eg, sustainability of donations or insufficient generic supplies. We advocate ten steps that need to be taken to improve access to safe and effective antifungal therapy for cryptococcal meningitis.
Journal Article > CommentaryFull Text
Lancet Infect Dis. 1 January 2021; Volume 21; DOI:10.1016/S1473-3099(20)30909-9
Shroufi A, Chiller T, Jordan A, Denning DW, Harrison TS, et al.
Lancet Infect Dis. 1 January 2021; Volume 21; DOI:10.1016/S1473-3099(20)30909-9
The UNAIDS target to reduce HIV-related death to fewer than 500 000 deaths per year by 2020 will not be met. 1 This statement might not be headline grabbing as this target was never as prominent as the 90-90-90 targets, 2 the achievement of which is a necessary but not sufficient step towards ending AIDS mortality.