Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Shroufi A[original query] |
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Induction-phase treatment costs for cryptococcal meningitis in high HIV-burden African countries: New opportunities with lower costs
Larson B , Shroufi A , Muthoga C , Oladele R , Rajasingham R , Jordan A , Jarvis JN , Chiller TM , Govender NP . Wellcome Open Res 12/28/2021 6 140 Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear. |
The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis
Rajasingham R , Govender NP , Jordan A , Loyse A , Shroufi A , Denning DW , Meya DB , Chiller TM , Boulware DR . Lancet Infect Dis 2022 22 (12) 1748-1755 BACKGROUND: Cryptococcal meningitis is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. The estimates of national, regional, and global burden of cryptococcal meningitis are essential to guide prevention strategies and determine needs for diagnostic tests and treatments. We present a 2020 estimate of the global burden of HIV-associated cryptococcal infection (antigenaemia), cryptococcal meningitis, and cryptococcal-associated deaths. METHODS: We defined advanced HIV disease as adults with a CD4 count of less than 200 cells/μL, as this group is at highest risk for cryptococcosis. We used UNAIDS estimates (2019-20) and population-based HIV impact assessment surveys (2016-18) to estimate the number of adults with CD4 counts of less than 200 cells/μL at risk for cryptococcosis, by country and region. Secondly, we summarised cryptococcal antigenaemia prevalence in those with a CD4 count of less than 200 cells/μL by reviewing published literature. Thereafter, we calculated the number of cryptococcal antigen (CrAg)-positive people in each country and region by multiplying the number with advanced HIV disease at risk for cryptococcal infection by the cryptococcal antigenaemia prevalence of the respective country or region. We estimated progression from cryptococcal antigenaemia to meningitis or death based on estimates from the published literature. FINDINGS: We estimated that there were 4·3 million (IQR 3·0-4·8) adults with HIV and CD4 counts of less than 200 cells/μL globally in 2020. We calculated a mean global cryptococcal antigenaemia prevalence of 4·4% (95% CI 1·6-7·4) among HIV-positive people with CD4 counts of less than 200 cells/μL, corresponding to 179 000 cases (IQR 133 000-219 000) of cryptococcal antigenaemia globally in 2020. Annually, we estimated that there are 152 000 cases (111 000-185 000) of cryptococcal meningitis, resulting in 112 000 cryptococcal-related deaths (79 000-134 000). Globally, cryptococcal disease accounts for 19% (13-24) of AIDS-related mortality. INTERPRETATION: Despite a reduction in the estimated absolute global burden of HIV-associated cryptococcal meningitis compared with 2014, likely to be due to antiretroviral therapy expansion, cryptococcal disease still accounts for 19% of AIDS-related deaths, similar to 2014 estimates. To end cryptococcal meningitis deaths by 2030, cryptococcal diagnostics, meningitis treatments, and implementation of preventive screening are urgently needed. FUNDING: None. |
Ending deaths from HIV-related cryptococcal meningitis by 2030
Shroufi A , Chiller T , Jordan A , Denning DW , Harrison TS , Govender NP , Loyse A , Baptiste S , Rajasingham R , Boulware DR , Ribeiro I , Jarvis JN , Van Cutsem G . Lancet Infect Dis 2020 21 (1) 16-18 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. | | The decline in HIV-related deaths is too slow. Early initiation of antiretroviral therapy (ART) for people living with HIV is the most important intervention for reducing HIV-related deaths. Access to ART for all is a distant goal in some settings due to ongoing challenges in identifying people with HIV and getting them on to treatment1 and ART alone isn’t enough to fully address HIV-related deaths. Among adults and adolescents, advanced HIV disease is diagnosed as a CD4 count of fewer than 200 cells per μL or a WHO stage 3 or 4 event.3 Evidence from South Africa shows more advanced HIV disease among ART-experienced people than among ART-naive people.4 Efforts to prevent disease progression will never replace the need for parallel improvements in the treatment of opportunistic infections. |
Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries
Loyse A , Burry J , Cohn J , Ford N , Chiller T , Ribeiro I , Koulla-Shiro S , Mghamba J , Ramadhani A , Nyirenda R , Aliyu SH , Wilson D , Le T , Oladele R , Lesikari S , Muzoora C , Kalata N , Temfack E , Mapoure Y , Sini V , Chanda D , Shimwela M , Lakhi S , Ngoma J , Gondwe-Chunda L , Perfect C , Shroufi A , Andrieux-Meyer I , Chan A , Schutz C , Hosseinipour M , Van der Horst C , Klausner JD , Boulware DR , Heyderman R , Lalloo D , Day J , Jarvis JN , Rodrigues M , Jaffar S , Denning D , Migone C , Doherty M , Lortholary O , Dromer F , Stack M , Molloy SF , Bicanic T , van Oosterhout J , Mwaba P , Kanyama C , Kouanfack C , Mfinanga S , Govender N , Harrison TS . Lancet Infect Dis 2018 19 (4) e143-e147 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. |
Cryptococcal antigen screening by lay cadres using a rapid test at the point of care: A feasibility study in rural Lesotho
Rick F , Niyibizi AA , Shroufi A , Onami K , Steele SJ , Kuleile M , Muleya I , Chiller T , Walker T , Van Cutsem G . PLoS One 2017 12 (9) e0183656 INTRODUCTION: Cryptococcal meningitis is one of the leading causes of death among people with HIV in Africa, primarily due to delayed presentation, poor availability and high cost of treatment. Routine cryptococcal antigen (CrAg) screening of patients with a CD4 count less than 100 cells/mm3, followed by pre-emptive therapy if positive, might reduce mortality in high prevalence settings. Using the cryptococcal antigen (CrAg) lateral flow assay (LFA), screening is possible at the point of care (POC). However, critical shortages of health staff may limit adoption. This study investigates the feasibility of lay counsellors conducting CrAg LFA screening in rural primary care clinics in Lesotho. METHODS: From May 2014 to June 2015, individuals who tested positive for HIV were tested for CD4 count and those with CD4 <100 cells/mm3 were screened with CrAg LFA. All tests were performed by lay counsellors. CrAg-positive asymptomatic patients received fluconazole, while symptomatic patients were referred to hospital. Lay counsellors were trained and supervised by a laboratory technician and counsellor activity supervisor. Additionally, nurses and doctors were trained on CrAg screening and appropriate treatment. RESULTS: During the study period, 1,388 people were newly diagnosed with HIV, of whom 129 (9%) presented with a CD4 count <100 cells/mm3. Of these, 128 (99%) were screened with CrAg LFA and 14/128 (11%) tested positive. Twelve of the 14 (86%) were asymptomatic, and received outpatient fluconazole. All commenced ART with a median time to initiation of 15.5 days [IQR: 14-22]. Of the asymptomatic patients, nine (75%) remained asymptomatic after a median time of 5 months [IQR; 3-6] of follow up. One (8%) became co-infected with tuberculosis and died and two were transferred out. The two patients with symptomatic cryptococcal meningitis (CM) were referred to hospital, where they later died. CONCLUSIONS: CrAg LFA screening by lay counsellors followed by pre-emptive fluconazole treatment for asymptomatic cases, or referral to hospital for symptomatic cases, proved feasible. However, regular follow-up to ensure proper management of cryptococcal disease was needed. These early results support the wider use of CrAg LFA screening in remote primary care settings where upper cadres of healthcare staff may be in short supply. |
Sustainable HIV treatment in Africa through viral-load-informed differentiated care
Phillips A , Shroufi A , Vojnov L , Cohn J , Roberts T , Ellman T , Bonner K , Rousseau C , Garnett G , Cambiano V , Nakagawa F , Ford D , Bansi-Matharu L , Miners A , Lundgren JD , Eaton JW , Parkes-Ratanshi R , Katz Z , Maman D , Ford N , Vitoria M , Doherty M , Dowdy D , Nichols B , Murtagh M , Wareham M , Palamountain KM , Chakanyuka Musanhu C , Stevens W , Katzenstein D , Ciaranello A , Barnabas R , Braithwaite RS , Bendavid E , Nathoo KJ , van de Vijver D , Wilson DP , Holmes C , Bershteyn A , Walker S , Raizes E , Jani I , Nelson LJ , Peeling R , Terris-Prestholt F , Murungu J , Mutasa-Apollo T , Hallett TB , Revill P . Nature 2015 528 (7580) S68-76 There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future. |
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- Page last updated:May 06, 2024
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