Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update

Govender, Nelesh P.; Meintjies, G; Bicanic, Tihana; Dawood, Halima; Harrison, Thomas S.; Jarvis, Joseph N; Karstaedt, Alan; Maartens, D.; McCarthy, Kerrigan; Rabie, Helena; Variava, Ebrahim; Venter, W D Francois; Boulware, David R.; Chiller, Tom; Meya, David B.; Scriven, James

doi:10.4102/sajhivmed.v14i2.82

Cited by 35 publications

(6 citation statements)

References 31 publications

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“…3 The South African clinical guidelines (2013) were followed for patients with positive plasma CrAg and negative CSF CrAg results. 10 ART was delayed for 2 weeks to decrease the risk of immune reconstitution inflammatory syndrome, and they were prescribed pre-emptive fluconazole oral treatment to prevent the development of meningeal infection. 10 Because of resource constraints, patients' cryptococcal infections were not verified using X-ray or other imaging technology, and we did not follow the individual patients' clinical course to collect outcome measures for the purposes of this study.…”

Section: Clinical Proceduresmentioning

confidence: 99%

Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014–2015

et al. 2020

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Background Cryptococcal meningitis is a leading cause of death amongst people living with HIV. However, routine cryptococcal antigen (CrAg) screening was not in the national guidelines in Eswatini. Objectives A cross-sectional study was conducted between August 2014 and March 2015 to examine CrAg prevalence at Mbabane Government Hospital in Eswatini. Methods We collected urine and whole blood from antiretroviral-therapy-naïve patients with HIV and a cluster of differentiation 4 (CD4) counts < 200 cells/mm 3 for plasma and urine CrAg lateral flow assay (LFA) screening at the national HIV reference laboratory. Two CD4 cut-off points were used to estimate CrAg prevalence: CD4 < 100 and < 200 cells/mm 3 . Sensitivity and specificity of urine CrAg LFA was compared to plasma CrAg LFA. Results Plasma CrAg prevalence was 4% (8/182, 95% confidence interval [CI]: 2–8) amongst patients with CD4 counts of < 200 cells/mm 3 , and 8% (8/102, 95% CI: 3–15) amongst patients with CD4 counts of < 100 cells/mm 3 . Urine CrAg LFA had a sensitivity of 100% (95% CI: 59–100) and a specificity of 80% (95% CI: 72–86) compared with plasma CrAg LFA tests for patients with CD4 < 200 cells/mm 3 . Forty-three per cent of 99 patients with CD4 < 100 were at World Health Organization clinical stages I or II. Conclusion The prevalence of CrAg in Eswatini was higher than the current global estimate of 6% amongst HIV-positive people with CD4 < 100 cell/mm 3 , indicating the importance of initiating a national screening programme. Mechanisms for CrAg testing, training, reporting, and drug and commodity supply issues are important considerations before national implementation.

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Section: Clinical Proceduresmentioning

confidence: 99%

Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014–2015

et al. 2020

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“…A lthough it has become easy to diagnose cryptococcal infections, even in resourcepoor settings (1)(2)(3)(4), treatment has largely remained difficult, due to current antifungal drugs being too expensive for some regions of the world. Importantly, the usage of some antifungal drugs is limited by their unintended side effects (5).…”

mentioning

confidence: 99%

Copper Acyl Salicylate Has Potential as an Anti-Cryptococcus Antifungal Agent

Ogundeji

Porotloane

Pohl

et al. 2018

Antimicrob Agents Chemother

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The antifungal activity of aspirin against cryptococcal cells has been reported. However, the unwanted effects of aspirin may limit its clinical application. Conceivably, a derivative of aspirin could overcome this challenge. Toward this end, this study considered the usage of an aspirinate-metal complex, namely, copper acyl salicylate (CAS), as an anti- antifungal agent. Additionally, the study examined the effects of this compound on macrophage function. The susceptibility results revealed that cryptococcal cells were vulnerable (in a dose-dependent manner) to CAS, which might have effected growth inhibition by damaging cryptococcal cell membranes. Interestingly, when CAS was used in combination with fluconazole or amphotericin B, synergism was observed. Furthermore, CAS did not negatively affect the growth or metabolic activity of macrophages; rather, it sensitized those immune cells to produce interferon gamma and interleukin 6, which, in turn, might have aided in the phagocytosis of cryptococcal cells. Compared to our aspirin data, CAS was noted to be more effective in killing cryptococcal cells (based on susceptibility results) and less toxic toward macrophages (based on growth inhibition results). Taking these findings together, it is reasonable to conclude that CAS may be a better anti- drug that could deliver better therapeutic outcomes, compared to aspirin.

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“…The initial (induction phase) management of HIV/CCM requires the following: (1) combination antifungal therapy including IV amphotericin B and oral flucytosine (first week only) and high-dose oral fluconazole 1200 mg daily (second week), after that an 8-week consolidation phase of oral fluconazole 800 mg daily, (2) control of raised intracranial pressure (rIP) with therapeutic lumbar punctures (LPs) to maintain the 'opening-pressure' (CSF-OP) at < 25 cm of water and (3) minimising the risk of immune reconstitution inflammatory syndrome (IRIS) by delaying the initiation of ART until 4 to 6 weeks after the start of antifungal therapy. 8,9,10,11,12 In the absence of a spinal manometer, the SA guidelines for the prevention, diagnosis and management of CCM recommend performing an LP to remove 20 mL -30 mL of CSF if the symptoms and signs of rIP are present. 12 However, in clinical practise only 23% -30% of CCM patients with signs and symptoms receive 'therapeutic' LPs.…”

Section: Read Onlinementioning

confidence: 99%

Intracranial pressure management in patients with human immunodeficiency virus-associated cryptococcal meningitis in a resource-constrained setting

Mkoko

Preez

Naidoo

2020

Southern African Journal of HIV Medicine

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Background Cryptococcal meningitis (CCM) is the leading cause of meningitis in people living with HIV (PLWH) in sub-Saharan Africa (SSA). The mortality and morbidity associated with CCM remain high. Combination of antifungal therapy, diligent management of intracranial pressure (IP) and the correct timing of the introduction of antiretroviral therapy (ART) minimise the risk of mortality and morbidity. The absence of spinal manometers in many healthcare centres in SSA challenges the accurate measurement of cerebrospinal fluid (CSF) pressure and its control. Objectives We hypothesised that four lumbar punctures (LPs) in the first week of the diagnosis and treatment of CCM would reduce IP such that in-hospital mortality and morbidity of HIV-associated CCM (HIV/CCM) would be significantly reduced. Methods We conducted a retrospective study to assess whether receipt of four or more LPs in the first week of the diagnosis and treatment with combination antifungal therapy of HIV/CCM would be associated with the reduction of in-hospital mortality in adult PLWH. Results From 01 January 2016 to 31 December 2016, 116 adult patients were admitted to the Dora Nginza District Hospital in Zwide, Port Elizabeth, South Africa. After exclusion of 11 (two were younger than 18 years, two had missing hospital records and seven demised or left the hospital before 7 days of hospitalisation), 105 patients were included in the analysis. The mean age was 39.4 (standard deviation [s.d.] ± 9.7) years, 64.8% were male. All were PLWH. A total of 52.4% had defaulted ART and 25.7% were ART naïve. Forty-three patients received four or more LPs (mean = 4.58 [± 0.96]) in the first week of hospitalisation with an associated in-hospital mortality of 11.6% ( n = 5/43) compared with 62 patients who received less than four LPs (mean = 2.18 [± 0.80]) with an in-hospital mortality of 29% ( n = 18/62) and a relative risk of 0.80 (95% CI, 0.66–0.97), p = 0.034. Conclusion In the current study of adult PLWH presenting to hospital with HIV/CCM, four or more LPs in the first 7 days following admission and the initiation of treatment were associated with a 17.4% reduction in absolute risk of in-hospital mortality and a 20% reduction in relative risk of in-hospital mortality. This mortality difference was noted in patients who survived and were in hospital at the time of the 7-day study census and persisted until the time of hospital discharge.

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Guideline for the prevention, diagnosis and management of cryptococcal meningitis among HIV-infected persons: 2013 update

Cited by 35 publications

References 31 publications

Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014–2015

Prevalence of cryptococcal antigen (CrAg) among HIV-positive patients in Eswatini, 2014–2015

Copper Acyl Salicylate Has Potential as an Anti-Cryptococcus Antifungal Agent

Intracranial pressure management in patients with human immunodeficiency virus-associated cryptococcal meningitis in a resource-constrained setting

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