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doi: 10.1097/QAD.0b013e328322ffac
Epidemiology and Social: Concise Communications

Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS

Park, Benjamin Ja; Wannemuehler, Kathleen Ab; Marston, Barbara Jc; Govender, Neleshd; Pappas, Peter Ge; Chiller, Tom Ma

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aMycotic Diseases Branch, USA

bBiostatistics Office, Division of Foodborne, Bacterial, and Mycotic Diseases, USA

cGlobal AIDS Program, Centers for Disease Control and Prevention, Atlanta, Georgia, USA

dMycology Reference Unit, National Institute for Communicable Diseases, Johannesburg, South Africa

eUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.

Received 23 July, 2008

Revised 5 November, 2008

Accepted 11 November, 2008

Correspondence to Dr Benjamin J. Park, 1600 Clifton Road, MS C-09, Atlanta, GA 30333, USA. Tel: +1 404 639 1619; e-mail:

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Objective: Cryptococcal meningitis is one of the most important HIV-related opportunistic infections, especially in the developing world. In order to help develop global strategies and priorities for prevention and treatment, it is important to estimate the burden of cryptococcal meningitis.

Design: Global burden of disease estimation using published studies.

Methods: We used the median incidence rate of available studies in a geographic region to estimate the region-specific cryptococcal meningitis incidence; this was multiplied by the 2007 United Nations Programme on HIV/AIDS HIV population estimate for each region to estimate cryptococcal meningitis cases. To estimate deaths, we assumed a 9% 3-month case-fatality rate among high-income regions, a 55% rate among low-income and middle-income regions, and a 70% rate in sub-Saharan Africa, based on studies published in these areas and expert opinion.

Results: Published incidence ranged from 0.04 to 12% per year among persons with HIV. Sub-Saharan Africa had the highest yearly burden estimate (median incidence 3.2%, 720 000 cases; range, 144 000–1.3 million). Median incidence was lowest in Western and Central Europe and Oceania (≤0.1% each). Globally, approximately 957 900 cases (range, 371 700–1 544 000) of cryptococcal meningitis occur each year, resulting in 624 700 deaths (range, 125 000–1 124 900) by 3 months after infection.

Conclusion: This study, the first attempt to estimate the global burden of cryptococcal meningitis, finds the number of cases and deaths to be very high, with most occurring in sub-Saharan Africa. Further work is needed to better define the scope of the problem and track the epidemiology of this infection, in order to prioritize prevention, diagnosis, and treatment strategies.

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Cryptococcal meningitis, a fungal infection caused by Cryptococcus spp., is one of the most important HIV-related opportunistic infections. In countries with a high HIV/AIDS prevalence, Cryptococcus is one of the most common causes of meningitis overall, more frequent than Streptococcus pneumoniae or Neisseria meningitidis [1–7]. Following the introduction of combination antiretroviral therapy (ART), the incidence of cryptococcosis has declined substantially in North America and Western Europe [8–11].

Understanding the burden of cryptococcal disease is particularly important for public health officials to adequately plan and prioritize needed resources for disease prevention and control. To better define the burden of cryptococcal meningitis, as it relates to other important diseases, and to understand the need for public health attention to this infection, we reviewed available epidemiological data and estimated the global burden of cryptococcal meningitis among persons living with HIV.

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Cryptococcal meningitis incidence data

We searched the published medical literature in November 2007 for eligible articles, using the search terms ‘HIV’ or ‘AIDS’ and ‘opportunistic infection,’ and limiting to studies published in English during or after 1996. An eligible article was one that utilized a prospective or retrospective cohort study design, was conducted in relatively varied heathcare settings (e.g., hospitalized and outpatient), and reported an incidence among persons with HIV or reported results from which incidence rates among persons with HIV could be calculated.

Our initial literature search yielded 9032 references. From these, we identified 19 studies that met our eligibility criteria [8–10,12–27]. Of the 19 studies, seven were population-based studies of large geographically defined areas [8,12,14,15,26,27]. The remaining 12 were provider-based studies that were not defined by geography [9,13,16–25].

Eleven studies directly reported an estimated incidence and in three [9,13,14] the incidence was determined based on data provided in a figure in the original article. For five population-based studies [8,10,12,15,27], the number of cases was reported but the incidence among persons with HIV was not. For three of these studies [8,12,15], we calculated the incidence rates in these areas using the number of cases reported as a numerator and using an available estimate for the total HIV population as a denominator. In one of these three [15], this numerator was the average yearly number of cases during the years of the surveillance, and, for the other two, we used the estimate for the final year of the study. For denominators, one study reported an estimate in the text [12], and, in another [15], we used a national surveillance report [28], and in the third [8], we used the 2007 United Nations Programme on HIV/AIDS (UNAIDS) estimate [29]. We excluded the other two population-based studies [10,27], because we were unable to determine the HIV population.

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Global HIV population data

The global population of persons living with HIV was taken from the estimate for prevalent cases of HIV among adults and children as reported in the 2007 UNAIDS report (33 200 000 cases) [29,30]. A separate HIV population estimate was taken for each of the UNAIDS regions.

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Regional and global estimates

We used the median incidence rate from the available studies of a geographic region, as defined by UNAIDS, to estimate the region-specific cryptococcal meningitis incidence. For regions with no available incidence data, we imputed the rate using the median from a region that is both geographically proximal and similar in economic development. Estimates of cryptococcal meningitis burden for each region i (CMi) were calculated by multiplying the median incidence rate by the 2007 UNAIDS HIV population estimate for each region [30]. The global burden estimate for cryptococcal meningitis was defined as the sum of all regional estimates.

The range of cases in each region was calculated as ±1 standard deviation (SD) from the regional estimate, in which the region-specific standard deviation SDi was defined as

Equation (Uncited)
Equation (Uncited)
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ĈV, was the median coefficient of variation of available region-specific CVis, and CMi was the estimate for cryptococcal meningitis cases in the region i. To determine ĈV, we first calculated the coefficient of variation (CVi) for each region with at least two available and differing data points using the median incidence and a robust estimate of scale based on the interquartile range. Because region-specific incidences were sparse, we pooled information across regions to estimate a common measure of variability, the median coefficient of variation (ĈV). This median coefficient of variation (ĈV) was then applied to each region to calculate the region-specific SDi. The estimation of SDi ignores the variability inherent in the estimate of the HIV counts. The SD for the global estimate was calculated as the square root of the sum of the squared SDis.

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Estimating case fatality

Because mortality is likely to vary regionally, we estimated deaths by using case-fatality rates from clinical trials conducted in developed and less-developed countries [31,32], by reviewing case series, surveillance reports, and reports on outcomes of cryptococcal meningitis [1,5,10,16,26,31,33–39], and by consulting with clinical experts (N.G., P.G.P.) in the care and outcomes of cryptococcal meningitis. In regions with primarily developed countries, we assumed a 10-week case-fatality rate of 9% among infected persons. Case fatality was estimated to be 55% in regions with primarily less-developed countries, excluding sub-Saharan Africa, where it was estimated to be 70%.

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Incidence reported in all studies ranged from 0.04 to 12% per year (Table 1). At least one eligible study was available from all regions except Eastern Europe and Central Asia; North Africa and Middle East; and the Caribbean. For these three regions, incidence rates were imputed: the rate in Eastern Europe and Central Asia, and North Africa and Middle East, were assumed to be the same as East Asia (1.7% per year). The incidence in the Caribbean was assumed to be the same as Latin America (3.4% per year).

Table 1
Table 1
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Using these rates, we estimated 957 900 (range, 371 700–1.54 million) cryptococcal meningitis cases occurred in 2006 (Table 1). The region with the highest number of estimated cases was sub-Saharan Africa (720 000 cases; range, 144 000–1.3 million), followed by South and South-east Asia (120 000 cases; range, 24 000–216 000). Oceania (100 cases), Western and Central Europe (500 cases), North Africa and Middle East (6500 cases), and North America (7800 cases) were the regions with the fewest.

On the basis of these estimates and the estimates of case fatality outlined above, approximately 624 725 deaths (range, 124 956–1,124 494) were associated with cryptococcal meningitis (Table 1); Oceania is estimated to have had the fewest (nine deaths), whereas sub-Saharan Africa had the most (504 000; range, 100 800–907 200). When comparing the estimate of deaths in sub-Saharan Africa with other diseases excluding HIV, deaths associated with cryptococcal meningitis are higher than tuberculosis (350 000) and approach the number related to childhood-cluster diseases (pertussis, poliomyelitis, diphtheria, measles, and tetanus, 530 000 deaths combined), diarrheal diseases (708 000), and malaria (1.1 million) (Fig. 1) [40].

Fig. 1
Fig. 1
Image Tools
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On the basis of review of available epidemiological data, we estimate a very substantial global burden of cryptococcal meningitis, both in terms of numbers of infections and associated deaths. These estimates will be useful for public health officials in designing and prioritizing efforts to prevent, diagnose, and treat cryptococcal disease.

The worldwide number of infections and deaths due to cryptococcal meningitis appear similar to those for diseases that have received greater public health attention. In sub-Saharan Africa, deaths due to cryptococcal meningitis (530 000) may be more frequent than tuberculosis (350 000) [40].

Our estimates of global disease burden are limited by the number of available studies in the literature and by the limitations of the original studies themselves. Provider-based cohort studies may not be representative of the region as a whole, and larger, population-based studies may be limited by incomplete follow-up or case ascertainment. For example, in one of the population-based studies from South Africa, the incidence was much lower than other studies from sub-Saharan Africa, likely due to incomplete case ascertainment [26].

We assumed case-fatality rates based on reviewing reports from clinical trials, surveillance studies, and expert opinion. Despite these assumptions, we feel that the number of deaths is fairly accurate, particularly in sub-Saharan Africa, as our estimate is consistent with what would be calculated from HIV cohort and natural history studies. These studies report that 13–44% of HIV/AIDS deaths are due to Cryptococcus [16,38,41]. If 2094 996 HIV/AIDS deaths occur annually in sub-Saharan Africa [40], then annual Cryptococcus-related deaths should range from 272 349 to 921 798.

Many of the incidence estimates used here were determined prior to the current effort to provide wide access to antiretroviral treatment. However, as the number of persons still needing antiretroviral drugs is likely to be stable or even increasing, due to the evolution of the HIV epidemic in many of these areas, expanding access to ART is not likely to impact the global burden of cryptococcal disease soon. In fact, rates of cryptococcal meningitis in South Africa have actually increased since the introduction of antiretroviral therapy [42], thereby emphasizing the growing and future need for attention to this problem.

In many of the developing countries in sub-Saharan Africa and South and South-east Asia, the capacity to perform the complicated management of severe cryptococcal meningitis is limited [43]. An important step in reducing the impact of this infection undoubtedly is the marked expansion of ARV access therapy for HIV, as risk of cryptococcal disease is substantially reduced among persons receiving these treatments. However, because the numbers of people with advanced immunosuppression from HIV and cryptococcal disease will continue to remain high despite expanded access to antiretroviral therapy, specific public health efforts are needed.

One such effort should be the expansion of laboratory diagnostic capacity for cryptococcal meningitis, such as India ink staining of cerebral spinal fluid, and the cryptococcal antigen latex agglutination test, which is simple to use, has high sensitivity and specificity [44], and requires little training for the proper use and interpretation.

Prevention of disease is the ultimate public health goal in the approach to cryptococcal meningitis, though this may be difficult to achieve. Although most clinical trials did not show a survival benefit [45–48], additional clinical trials are warranted, especially in sub-Saharan Africa, where the incidence of cryptococcal meningitis is high and outcomes of infection are poor. Another strategy that warrants further investigation is screening for early cryptococcal disease with the serum cryptococcal antigen test. Nonmeningeal cryptococcal infection often precedes meningitis but is underrecognized or misdiagnosed [16,35,49–51]. Early detection and treatment of asymptomatic or latent cryptococcal infection may allow for fluconazole to be used as the first-line therapy, a much less expensive and highly available option.

Our findings underscore the tremendous burden of cryptococcal meningitis, as well as the critical need for a better understanding of its epidemiology in developing countries with large numbers of persons living with HIV/AIDS. A focused effort to improve diagnostic capacity, expand treatment options, and identify effective measures for prevention of cryptococcal disease is urgently needed.

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The findings and conclusions in this presentation/report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

This information is distributed solely for the purpose of predissemination peer review under applicable information quality guidelines. It has not been formally disseminated by the Centers for Disease Control and Prevention. It does not represent and should not be construed to represent any agency determination or policy.

Funding source: This study was conducted while being employed by the US Government; no external funds were used for this study.

P.G.P. has received a research grant, is a member of speakers' bureau, and is an ad hoc advisor (Pfizer, Merck, Astellas) and has received a research grant and is an ad hoc advisor (Schering-Plough).

B.J.P., K.A.W., B.J. M., N.G., T.M.C. have no conflicts of interest.

Conception and design were done by B.J.P., K.A.W., B.J.M., N.G., P.G.P., T.M.C.

Acquisition of data was done by B.J.P., K.A.W.

Analysis and interpretation of data was done by B.J.P., K.A.W., B.J.M., N.G., P.G.P., T.M.C.

Drafting of manuscript was done by B.J.P., K.A.W., B.J.M., T.M.C.

Critical review of manuscript was done by B.J.P., K.A.W., B.J.M., N.G., P.G.P., T.M.C.

Statistical analysis was done by B.J.P., K.A.W.

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Clinical Infectious Diseases
Clinical Practice Guidelines for the Management of Cryptococcal Disease: 2010 Update by the Infectious Diseases Society of America
Perfect, JR; Dismukes, WE; Dromer, F; Goldman, DL; Graybill, JR; Hamill, RJ; Harrison, TS; Larsen, RA; Lortholary, O; Nguyen, MH; Pappas, PG; Powderly, WG; Singh, N; Sobel, JD; Sorrell, TC
Clinical Infectious Diseases, 50(3): 291-322.
Journal of Clinical Investigation
Pathogen-specific antibodies: codependent no longer
Janoff, EN; Frank, DN
Journal of Clinical Investigation, 120(4): 1039-1042.
Vesicle-associated melanization in Cryptococcus neoformans
Eisenman, HC; Frases, S; Nicola, AM; Rodrigues, ML; Casadevall, A
Microbiology-Sgm, 155(): 3860-3867.
Plos One
Microsatellite Typing of Clinical and Environmental Cryptococcus neoformans var. grubii Isolates from Cuba Shows Multiple Genetic Lineages
Illnait-Zaragozi, MT; Martinez-Machin, GF; Fernandez-Andreu, CM; Boekhout, T; Meis, JF; Klaassen, CHW
Plos One, 5(2): -.
ARTN e9124
Expert Opinion on Pharmacotherapy
Pharmacotherapy of cryptococcosis
Ritter, M; Goldman, DL
Expert Opinion on Pharmacotherapy, 10(): 2433-2443.
Cellular Microbiology
Cryptococcus neoformans responds to mannitol by increasing capsule size in vitro and in vivo
Guimaraes, AJ; Frases, S; Cordero, RJB; Nimrichter, L; Casadevall, A; Nosanchuk, JD
Cellular Microbiology, 12(6): 740-753.
Eukaryotic Cell
Isolation and Characterization of Senescent Cryptococcus neoformans and Implications for Phenotypic Switching and Pathogenesis in Chronic Cryptococcosis
Jain, N; Cook, E; Xess, I; Hasan, F; Fries, D; Fries, BC
Eukaryotic Cell, 8(6): 858-866.
Medical Mycology
Voriconazole use and pharmacokinetics in combination with interferon-gamma for refractory cryptococcal meningitis in a patient receiving low-dose ritonavir
Nierenberg, NE; Thompson, GR; Lewis, JS; Hogan, BK; Patterson, TF
Medical Mycology, 48(3): 532-536.
Future Microbiology
Variability of phenotypic traits in Cryptococcus varieties and species and the resulting implications for pathogenesis
Gupta, G; Fries, BC
Future Microbiology, 5(5): 775-787.
Nature Reviews Microbiology
SCIENCE AND SOCIETY Microbial threat lists: obstacles in the quest for biosecurity?
Casadevall, A; Relman, DA
Nature Reviews Microbiology, 8(2): 149-154.
Emerging Infectious Diseases
Projecting Global Occurrence of Cryptococcus gattii
Springer, DJ; Chaturvedi, V
Emerging Infectious Diseases, 16(1): 14-20.
Plos Pathogens
Emergence and Pathogenicity of Highly Virulent Cryptococcus gattii Genotypes in the Northwest United States
Byrnes, EJ; Li, WJ; Lewit, Y; Ma, HS; Voelz, K; Ren, P; Carter, DA; Chaturvedi, V; Bildfell, RJ; May, RC; Heitman, J
Plos Pathogens, 6(4): -.
ARTN e1000850
Eukaryotic Cell
A Putative P-Type ATPase, Apt1, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans
Hu, GG; Kronstad, JW
Eukaryotic Cell, 9(1): 74-83.
Journal of Clinical Investigation
Cryptococci at the brain gate: break and enter or use a Trojan horse?
Casadevall, A
Journal of Clinical Investigation, 120(5): 1389-1392.
Eukaryotic Cell
Cryptococcal Interactions with the Host Immune System
Voelz, K; May, RC
Eukaryotic Cell, 9(6): 835-846.
Clinical Infectious Diseases
A Phase II Randomized Trial of Amphotericin B Alone or Combined with Fluconazole in the Treatment of HIV-Associated Cryptococcal Meningitis
Pappas, PG; Chetchotisakd, P; Larsen, RA; Manosuthi, W; Morris, MI; Anekthananon, T; Sungkanuparph, S; Supparatpinyo, K; Nolen, TL; Zimmer, LO; Kendrick, AS; Johnson, P; Sobel, JD; Filler, SG
Clinical Infectious Diseases, 48(): 1775-1783.
Infection and Immunity
Improved Survival of Mice Deficient in Secretory Immunoglobulin M following Systemic Infection with Cryptococcus neoformans
Subramaniam, KS; Datta, K; Marks, MS; Pirofski, LA
Infection and Immunity, 78(1): 441-452.
Annual Review of Microbiology
How Sweet it is! Cell Wall Biogenesis and Polysaccharide Capsule Formation in Cryptococcus neoformans
Doering, TL
Annual Review of Microbiology, 63(): 223-247.
Plos One
Treatment of Cryptococcal Meningitis in KwaZulu-Natal, South Africa
Lightowler, JVJ; Cooke, GS; Mutevedzi, P; Lessells, RJ; Newell, ML; Dedicoat, M
Plos One, 5(1): -.
ARTN e8630
Chinese Medical Journal
Cryptococcus gattii infections in China: extent of the problem?
Chen, M; Pan, WH; Boekhout, T
Chinese Medical Journal, 126(2): 203-205.
Biochimica Et Biophysica Acta-Biomembranes
Structural and functional studies on a proline-rich peptide isolated from swine saliva endowed with antifungal activity towards Cryptococcus neoformans
Conti, S; Radicioni, G; Ciociola, T; Longhi, R; Polonelli, L; Gatti, R; Cabras, T; Messana, I; Castagnola, M; Vitali, A
Biochimica Et Biophysica Acta-Biomembranes, 1828(3): 1066-1074.
Plos One
Induction of Brain Microvascular Endothelial Cell Urokinase Expression by Cryptococcus neoformans Facilitates Blood-Brain Barrier Invasion
Stie, J; Fox, D
Plos One, 7(): -.
ARTN e49402
Immunological Reviews
HIV and co-infections
Chang, CC; Crane, M; Zhou, JL; Mina, M; Post, JJ; Cameron, BA; Lloyd, AR; Jaworowski, A; French, MA; Lewin, SR
Immunological Reviews, 254(): 114-142.
Plos One
Characterization of the Complete Uric Acid Degradation Pathway in the Fungal Pathogen Cryptococcus neoformans
Lee, IR; Yang, LT; Sebetso, G; Allen, R; Doan, THN; Blundell, R; Lui, EYL; Morrow, CA; Fraser, JA
Plos One, 8(5): -.
ARTN e64292
International Immunology
Abrogation of IL-4 receptor-alpha-dependent alternatively activated macrophages is sufficient to confer resistance against pulmonary cryptococcosis despite an ongoing T(h)2 response
Muller, U; Stenzel, W; Piehler, D; Grahnert, A; Protschka, M; Kohler, G; Frey, O; Held, J; Richter, T; Eschke, M; Kamradt, T; Brombacher, F; Alber, G
International Immunology, 25(8): 459-470.
Cell Research
Biofilm from a clinical strain of Cryptococcus neoformans activates the NLRP3 inflammasome
Lei, GW; Chen, MK; Li, H; Niu, JL; Wu, SX; Mao, LM; Lu, AL; Wang, HB; Chen, W; Xu, B; Leng, QB; Xu, CS; Yang, GW; An, LG; Zhu, LP; Meng, GX
Cell Research, 23(7): 965-968.
Infection and Immunity
Cryptococcus neoformans Requires the ESCRT Protein Vps23 for Iron Acquisition from Heme, for Capsule Formation, and for Virulence
Hu, GG; Caza, M; Cadieux, B; Chan, V; Liu, V; Kronstad, J
Infection and Immunity, 81(1): 292-302.
Infection and Immunity
Cryptococcus neoformans Growth and Protection from Innate Immunity Are Dependent on Expression of a Virulence-Associated DEAD-Box Protein, Vad1
Qiu, J; Olszewski, MA; Williamson, PR
Infection and Immunity, 81(3): 777-788.
Infection and Immunity
Altered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 Transgene
Leongson, K; Cousineau-Cote, V; Goupil, M; Aumont, F; Senechal, S; Gaboury, L; Jolicoeur, P; Kronstad, JW; de Repentigny, L
Infection and Immunity, 81(4): 1100-1113.
Journal of Neurovirology
Neurovirulence of Cryptococcus neoformans determined by time course of capsule accumulation and total volume of capsule in the brain
Pool, A; Lowder, L; Wu, Y; Forrester, K; Rumbaugh, J
Journal of Neurovirology, 19(3): 228-238.
Plos One
A Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, Malawi
Rothe, C; Sloan, DJ; Goodson, P; Chikafa, J; Mukaka, M; Denis, B; Harrison, T; van Oosterhout, JJ; Heyderman, RS; Lalloo, DG; Allain, T; Feasey, NA
Plos One, 8(6): -.
ARTN e67311
Brazilian Journal of Infectious Diseases
Strategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin America
Vidal, JE; de Oliveira, ACP; Dauar, RF; Boulware, DR
Brazilian Journal of Infectious Diseases, 17(3): 353-362.
Journal of Infection
The prevalence of cryptococcal antigenemia in newly diagnosed HIV patients in a Southwest London cohort
Patel, S; Shin, GY; Wijewardana, I; Vitharana, SR; Cormack, I; Pakianathan, M; Harrison, TS; Bicanic, T
Journal of Infection, 66(1): 75-79.
Current Medical Research and Opinion
Fungal diagnosis: how do we do it and can we do better?
Perfect, JR
Current Medical Research and Opinion, 29(): 3-11.
A copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformans
Raja, MR; Waterman, SR; Qiu, J; Bleher, R; Williamson, PR; O'Halloran, TV
Metallomics, 5(4): 363-371.
Evolution of fungal sexual reproduction
Heitman, J; Sun, S; James, TY
Mycologia, 105(1): 1-27.
Fungal Virulence in a Lepidopteran Model Is an Emergent Property with Deterministic Features
Garcia-Solache, MA; Izquierdo-Garcia, D; Smith, C; Bergman, A; Casadevalla, A
Mbio, 4(3): -.
ARTN e00100-13
Macrophage M1/M2 Polarization Dynamically Adapts to Changes in Cytokine Microenvironments in Cryptococcus neoformans Infection
Davis, MJ; Tsang, TM; Qiu, YF; Dayrit, JK; Freij, JB; Huffnagle, GB; Olszewski, MA
Mbio, 4(3): -.
ARTN e00264-13
Plos One
Clinical Utility of the Cryptococcal Antigen Lateral Flow Assay in a Diagnostic Mycology Laboratory
McMullan, BJ; Halliday, C; Sorrell, TC; Judd, D; Sleiman, S; Marriott, D; Olma, T; Chen, SCA
Plos One, 7(): -.
ARTN e49541
New England Journal of Medicine
Combination Antifungal Therapy for Cryptococcal Meningitis
Day, JN; Chau, TTH; Wolbers, M; Mai, PP; Dung, NT; Mai, NH; Phu, NH; Nghia, HD; Phong, ND; Thai, CQ; Thai, LH; Chuong, LV; Sinh, DX; Duong, VA; Hoang, TN; Diep, PT; Campbell, JI; Sieu, TPM; Baker, SG; Chau, NVV; Hien, TT; Lalloo, DG; Farrar, JJ
New England Journal of Medicine, 368(): 1291-1302.
New England Journal of Medicine
Efficiently Killing a Sugar-Coated Yeast
Perfect, JR
New England Journal of Medicine, 368(): 1354-1356.
Eukaryotic Cell
Cryptococcus neoformans Phosphoinositide-Dependent Kinase 1 (PDK1) Ortholog Is Required for Stress Tolerance and Survival in Murine Phagocytes
Chabrier-Rosello, Y; Gerik, KJ; Koselny, K; DiDone, L; Lodge, JK; Krysan, DJ
Eukaryotic Cell, 12(1): 12-22.
Eukaryotic Cell
Role of Cryptococcus neoformans Rho1 GTPases in the PKC1 Signaling Pathway in Response to Thermal Stress
Lam, WC; Gerik, KJ; Lodge, JK
Eukaryotic Cell, 12(1): 118-131.
Plos One
Epidemiology of Cryptococcal Meningitis in the US: 1997-2009
Pyrgos, V; Seitz, AE; Steiner, CA; Prevots, DR; Williamson, PR
Plos One, 8(2): -.
ARTN e56269
Japanese Journal of Infectious Diseases
Determination of Epidemiology of Clinically Isolated Cryptococcus neoformans Strains in Japan by Multi locus Sequence Typing
Umeyama, T; Ohno, H; Minamoto, F; Takagi, T; Tanamachi, C; Tanabe, K; Kaneko, Y; Yamagoe, S; Kishi, K; Fujii, T; Takemura, H; Watanabe, H; Miyazaki, Y
Japanese Journal of Infectious Diseases, 66(1): 51-55.

Biochemical and Biophysical Research Communications
3-Bromopyruvate: A novel antifungal agent against the human pathogen Cryptococcus neoformans
Dylag, M; Lis, P; Niedwiecka, K; Ko, YH; Pedersen, PL; Goffeau, A; Ulaszewski, S
Biochemical and Biophysical Research Communications, 434(2): 322-327.
Journal of the Brazilian Chemical Society
2D Chemometric Studies of a Series of Azole Derivatives Active against Fluconazole-Resistant Cryptococcus gattii
Freitas, HF; Barros, TF; Castilho, MS
Journal of the Brazilian Chemical Society, 24(6): 962-U889.
Journal of Immunology
IL-33 Signaling Regulates Innate and Adaptive Immunity to Cryptococcus neoformans
Flaczyk, A; Duerr, CU; Shourian, M; Lafferty, EI; Fritz, JH; Qureshi, ST
Journal of Immunology, 191(5): 2503-2513.
Mucosal Immunology
T1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosis
Piehler, D; Grahnert, A; Eschke, M; Richter, T; Kohler, G; Stenzel, W; Alber, G
Mucosal Immunology, 6(2): 405-414.
Plos One
Evidence for Mitotic Recombination within the Basidia of a Hybrid Cross of Cryptococcus neoformans
Vogan, AA; Khankhet, J; Xu, JP
Plos One, 8(5): -.
ARTN e62790
Analytical and Bioanalytical Chemistry
A high-throughput screening assay for assessing the viability of Cryptococcus neoformans under nutrient starvation conditions
Dehdashti, SJ; Abbott, J; Nguyen, DT; McKew, JC; Williamson, PR; Zheng, W
Analytical and Bioanalytical Chemistry, 405(): 6823-6829.
Future Microbiology
Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells
Bryan, RA; Jiang, ZW; Morgenstern, A; Bruchertseifer, F; Casadevall, A; Dadachova, E
Future Microbiology, 8(9): 1081-1089.
Cellular Microbiology
Cryptococcus interactions with macrophages: evasion and manipulation of the phagosome by a fungal pathogen
Johnston, SA; May, RC
Cellular Microbiology, 15(3): 403-411.
Plos One
High Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in Ethiopia
Alemu, AS; Kempker, RR; Tenna, A; Smitson, C; Berhe, N; Fekade, D; Blumberg, HM; Aseffa, A
Plos One, 8(3): -.
ARTN e58377
Postgraduate Medical Journal
Predictors of outcome in routine care for Cryptococcal meningitis in Western Kenya: lessons for HIV outpatient care in resource-limited settings
Kendi, C; Penner, J; Koech, J; Nyonda, M; Cohen, CR; Bukusi, EA; Ngugi, E; Meyer, ACL
Postgraduate Medical Journal, 89(): 73-77.
Plos One
Long Term 5-Year Survival of Persons with Cryptococcal Meningitis or Asymptomatic Subclinical Antigenemia in Uganda
Butler, EK; Boulware, DR; Bohjanen, PR; Meya, DB
Plos One, 7(): -.
ARTN e51291
Trends in Microbiology
Can host receptors for fungi be targeted for treatment of fungal infections?
Filler, SG
Trends in Microbiology, 21(8): 389-396.
Clinical Infectious Diseases
Rapidly Progressive Skin Lesions Requiring Admission in a Young, HIV-Infected Man
Klein, CN; Mohanraj, BS; Musial, R; Popnikolov, N; Vielemeyer, O
Clinical Infectious Diseases, 56(1): 117-+.
Plos Biology
Unisexual and Heterosexual Meiotic Reproduction Generate Aneuploidy and Phenotypic Diversity De Novo in the Yeast Cryptococcus neoformans
Ni, M; Feretzaki, M; Li, WJ; Floyd-Averette, A; Mieczkowski, P; Dietrich, FS; Heitman, J
Plos Biology, 11(9): -.
ARTN e1001653
Tropical Medicine & International Health
Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa
Fenner, L; Reid, SE; Fox, MP; Garone, D; Wellington, M; Prozesky, H; Zwahlen, M; Schomaker, M; Wandeler, G; Kancheya, N; Boulle, A; Wood, R; Henostroza, G; Egger, M
Tropical Medicine & International Health, 18(2): 194-198.
Antimicrobial Agents and Chemotherapy
Limited Activity of Miltefosine in Murine Models of Cryptococcal Meningoencephalitis and Disseminated Cryptococcosis
Wiederhold, NP; Najvar, LK; Bocanegra, R; Kirkpatrick, WR; Sorrell, TC; Patterson, TF
Antimicrobial Agents and Chemotherapy, 57(2): 745-750.
Biochemical Society Transactions
Mechanisms of microbial escape from phagocyte killing
Smith, LM; May, RC
Biochemical Society Transactions, 41(): 475-490.
Antimicrobial Agents and Chemotherapy
Pharmacokinetics and Pharmacodynamics of Fluconazole for Cryptococcal Meningoencephalitis: Implications for Antifungal Therapy and In Vitro Susceptibility Breakpoints
Sudan, A; Livermore, J; Howard, SJ; Al-Nakeeb, Z; Sharp, A; Goodwin, J; Gregson, L; Warn, PA; Felton, TW; Perfect, JR; Harrison, TS; Hope, WW
Antimicrobial Agents and Chemotherapy, 57(6): 2793-2800.
Journal of Biological Chemistry
Unusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformans
Heiss, C; Skowyra, ML; Liu, H; Klutts, JS; Wang, ZR; Williams, M; Srikanta, D; Beverley, SM; Azadi, P; Doering, TL
Journal of Biological Chemistry, 288(): 10994-11003.
Future Microbiology
Exserohilum rostratum fungal meningitis associated with methylprednisolone injections
Casadevall, A; Pirofski, LA
Future Microbiology, 8(2): 135-137.
Trends in Microbiology
An encapsulation of iron homeostasis and virulence in Cryptococcus neoformans
Kronstad, JW; Hu, G; Jung, WH
Trends in Microbiology, 21(9): 457-465.
Plos One
Cryptococcus gattii Induces a Cytokine Pattern That Is Distinct from Other Cryptococcal Species
Schoffelen, T; Illnait-Zaragozi, MT; Joosten, LAB; Netea, MG; Boekhout, T; Meis, JF; Sprong, T
Plos One, 8(1): -.
ARTN e55579
Cryptococcal Infections: Changing Epidemiology and Implications for Therapy
La Hoz, RM; Pappas, PG
Drugs, 73(6): 495-504.
Cryptococcus neoformans Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune Responses
O'Meara, TR; Holmer, SM; Selvig, K; Dietrich, F; Alspaugh, JA
Mbio, 4(1): -.
ARTN e00522-12
Molecular Microbiology
Uncoupling of mRNA synthesis and degradation impairs adaptation to host temperature in Cryptococcus neoformans
Bloom, ALM; Solomons, JTG; Havel, VE; Panepinto, JC
Molecular Microbiology, 89(1): 65-83.
International Journal of Antimicrobial Agents
Evaluation of the anticryptococcal activity of the antibiotic polymyxin B in vitro and in vivo
Zhai, B; Lin, XR
International Journal of Antimicrobial Agents, 41(3): 250-254.
Tropical Medicine & International Health
The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya
Meyer, ACL; Kendi, CK; Penner, JA; Odhiambo, N; Otieno, B; Omondi, E; Opiyo, E; Bukusi, EA; Cohen, CR
Tropical Medicine & International Health, 18(4): 495-503.
African Health Sciences
Challenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settings
Musubire, AK; Meya, BD; Mayanja-Kizza, H; Lukande, R; Wiesner, LD; Bohjanen, P; Boulware, RD
African Health Sciences, 12(2): 226-230.
Clinical and Vaccine Immunology
Serotype Sensitivity of a Lateral Flow Immunoassay for Cryptococcal Antigen
Gates-Hollingsworth, MA; Kozel, TR
Clinical and Vaccine Immunology, 20(4): 634-635.
Journal of Immunology
Scavenger Receptor A Modulates the Immune Response to Pulmonary Cryptococcus neoformans Infection
Qiu, YF; Dayrit, JK; Davis, MJ; Carolan, JF; Osterholzer, JJ; Curtis, JL; Olszewski, MA
Journal of Immunology, 191(1): 238-248.
Plos One
Global Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative Stress
Upadhya, R; Campbell, LT; Donlin, MJ; Aurora, R; Lodge, JK
Plos One, 8(1): -.
ARTN e55110
G3-Genes Genomes Genetics
Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii
Chen, YL; Lehman, VN; Lewit, Y; Averette, AF; Heitman, J
G3-Genes Genomes Genetics, 3(3): 527-539.
Plos One
Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa
Drain, PK; Losina, E; Parker, G; Giddy, J; Ross, D; Katz, JN; Coleman, SM; Bogart, LM; Freedberg, KA; Walensky, RP; Bassett, IV
Plos One, 8(1): -.
ARTN e55305
Arhiv Za Higijenu Rada I Toksikologiju
Two Rare Cases of Central Nervous System Opportunistic Mycoses
Missoni, EM; Barsic, B
Arhiv Za Higijenu Rada I Toksikologiju, 63(4): 505-511.
Plos One
Prevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program - Vietnam
Smith, RM; Nguyen, TA; Ha, HTT; Thang, PH; Thuy, C; Lien, TX; Bui, HT; Le, TH; Struminger, B; McConnell, MS; Fanfair, RN; Park, BJ; Harris, JR
Plos One, 8(4): -.
ARTN e62213
Clinical Infectious Diseases
Reconsidering Cryptococcal Antigen Screening in the US Among Persons With CD4 < 100 cells/mcL
Rajasingham, R; Boulware, DR
Clinical Infectious Diseases, 55(): 1742-1744.
Current Opinion in Microbiology
Progress in understanding fungal pathogenesis
Casadevall, A
Current Opinion in Microbiology, 16(4): 375-376.
Current Opinion in Microbiology
Vesicular mechanisms of traffic of fungal molecules to the extracellular space
Rodrigues, ML; Franzen, AJ; Nimrichter, L; Miranda, K
Current Opinion in Microbiology, 16(4): 414-420.
Tropical Medicine & International Health
Cryptococcal antigen prevalence in HIV-infected Tanzanians: a cross-sectional study and evaluation of a point-of-care lateral flow assay
Rugemalila, J; Maro, VP; Kapanda, G; Ndaro, AJ; Jarvis, JN
Tropical Medicine & International Health, 18(9): 1075-1079.
Clinical Infectious Diseases
Early Versus Delayed Antiretroviral Therapy and Cerebrospinal Fluid Fungal Clearance in Adults With HIV and Cryptococcal Meningitis
Bisson, GP; Molefi, M; Bellamy, S; Thakur, R; Steenhoff, A; Tamuhla, N; Rantleru, T; Tsimako, I; Gluckman, S; Ravimohan, S; Weissman, D; Tebas, P
Clinical Infectious Diseases, 56(8): 1165-1173.
Journal of Infectious Diseases
The Mannoprotein Cig1 Supports Iron Acquisition From Heme and Virulence in the Pathogenic Fungus Cryptococcus neoformans
Cadieux, B; Lian, TS; Hu, GG; Wang, J; Biondo, C; Teti, G; Liu, V; Murphy, MEP; Creagh, AL; Kronstad, JW
Journal of Infectious Diseases, 207(8): 1339-1347.
European Journal of Clinical Microbiology & Infectious Diseases
Antifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin B
Cordeiro, RD; Mourao, CI; Rocha, MFG; Marques, FJD; Teixeira, CEC; Miranda, DFD; Neto, LVP; Brilhante, RSN; Bandeira, TDPG; Sidrim, JJC
European Journal of Clinical Microbiology & Infectious Diseases, 32(4): 557-564.
Plos Pathogens
Emerging Infectious Diseases: Threats to Human Health and Global Stability
Morens, DM; Fauci, AS
Plos Pathogens, 9(7): -.
ARTN e1003467
Plos Pathogens
Brain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain Barrier
Liu, TB; Kim, JC; Wang, YN; Toffaletti, DL; Eugenin, E; Perfect, JR; Kim, KJ; Xue, CY
Plos Pathogens, 9(4): -.
ARTN e1003247
Journal of Infectious Diseases
Pharmacodynamics of Liposomal Amphotericin B and Flucytosine for Cryptococcal Meningoencephalitis: Safe and Effective Regimens for Immunocompromised Patients
O'Connor, L; Livermore, J; Sharp, AD; Goodwin, J; Gregson, L; Howard, SJ; Felton, TW; Schwartz, JA; Neely, MN; Harrison, TS; Perfect, JR; Hope, WW
Journal of Infectious Diseases, 208(2): 351-361.
Science Translational Medicine
Hidden Killers: Human Fungal Infections
Brown, GD; Denning, DW; Gow, NAR; Levitz, SM; Netea, MG; White, TC
Science Translational Medicine, 4(): -.
ARTN 165rv13
Cryptococcosis in Colombia: Results of the national surveillance program for the years 2006-2010
Escandon, P; de Bedout, C; Lizarazo, J; Agudelo, CI; Tobon, A; Bello, S; Restrepo, A; Castaneda, E
Biomedica, 32(3): 386-398.
G3-Genes Genomes Genetics
Comparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene Associated With Carbon Utilization and Virulence
Ormerod, KL; Morrow, CA; Chow, EWL; Lee, IR; Arras, SDM; Schirra, HJ; Cox, GM; Fries, BC; Fraser, JA
G3-Genes Genomes Genetics, 3(4): 675-686.
Journal of Infectious Diseases
Advancing Translational Immunology in HIV-Associated Cryptococcal Meningitis
Williamson, PR
Journal of Infectious Diseases, 207(): 1793-1795.
Journal of Infectious Diseases
The Phenotype of the Cryptococcus-Specific CD4(+) Memory T-Cell Response Is Associated With Disease Severity and Outcome in HIV-Associated Cryptococcal Meningitis
Jarvis, JN; Casazza, JP; Stone, HH; Meintjes, G; Lawn, SD; Levitz, SM; Harrison, TS; Koup, RA
Journal of Infectious Diseases, 207(): 1817-1828.
Molecular Microbiology
Allergen1 regulates polysaccharide structure in Cryptococcus neoformans
Jain, N; Cordero, RJB; Casadevall, A; Fries, BC
Molecular Microbiology, 88(4): 713-727.
Plos One
Predictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune Status
Brizendine, KD; Baddley, JW; Pappas, PG
Plos One, 8(3): -.
ARTN e60431
Journal of Infectious Diseases
Cryptococcosis-IRIS is Associated With Lower Cryptococcus-specific IFN-gamma Responses Before Antiretroviral Therapy but Not Higher T-Cell Responses During Therapy
Chang, CC; Lim, A; Omarjee, S; Levitz, SM; Gosnell, BI; Spelman, T; Elliott, JH; Carr, WH; Moosa, MYS; Ndung'u, T; Lewin, SR; French, MA
Journal of Infectious Diseases, 208(6): 898-906.
Plos One
Cost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South Africa
Jarvis, JN; Harrison, TS; Lawn, SD; Meintjes, G; Wood, R; Cleary, S
Plos One, 8(7): -.
ARTN e69288
Infection and Immunity
Cryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial Cells
Vu, K; Eigenheer, RA; Phinney, BS; Gelli, A
Infection and Immunity, 81(9): 3139-3147.
Molecular Microbiology
A defect in ATP-citrate lyase links acetyl-CoA production, virulence factor elaboration and virulence in Cryptococcus neoformans
Griffiths, EJ; Hu, GG; Fries, B; Caza, M; Wang, J; Gsponer, J; Gates-Hollingsworth, MA; Kozel, TR; De Repentigny, L; Kronstad, JW
Molecular Microbiology, 86(6): 1404-1423.
Infection and Immunity
Congenic Strains for Genetic Analysis of Virulence Traits in Cryptococcus gattii
Zhu, PK; Zhai, B; Lin, XR; Idnurm, A
Infection and Immunity, 81(7): 2616-2625.
Infection and Immunity
Congenic Strains of the Filamentous Form of Cryptococcus neoformans for Studies of Fungal Morphogenesis and Virulence
Zhai, B; Zhu, PK; Foyle, D; Upadhyay, S; Idnurm, A; Lin, XR
Infection and Immunity, 81(7): 2626-2637.
Applied and Environmental Microbiology
Susceptibility of Intact Germinating Arabidopsis thaliana to Human Fungal Pathogens Cryptococcus neoformans and C. gattii
Warpeha, KM; Park, YD; Williamson, PR
Applied and Environmental Microbiology, 79(9): 2979-2988.
Journal of Infectious Diseases
Methamphetamine Alters Blood Brain Barrier Protein Expression in Mice, Facilitating Central Nervous System Infection by Neurotropic Cryptococcus neoformans
Eugenin, EA; Greco, JM; Frases, S; Nosanchuk, JD; Martinez, LR
Journal of Infectious Diseases, 208(4): 699-704.
Infection and Immunity
Requirement and Redundancy of the Src Family Kinases Fyn and Lyn in Perforin-Dependent Killing of Cryptococcus neoformans by NK Cells
Oykhman, P; Timm-McCann, M; Xiang, RF; Islam, A; Li, SS; Stack, D; Huston, SM; Ma, LL; Mody, CH
Infection and Immunity, 81(): 3912-3922.
Histopathology of the arachnoid granulations and brain in HIV-associated cryptococcal meningitis: correlation with cerebrospinal fluid pressure
Loyse, A; Wainwright, H; Jarvis, JN; Bicanic, T; Rebe, K; Meintjes, G; Harrison, TS
AIDS, 24(3): 405-410.
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Is HIV-associated tuberculosis a risk factor for the development of cryptococcal disease?
Jarvis, JN; Harrison, TS; Corbett, EL; Wood, R; Lawn, SD
AIDS, 24(4): 612-614.
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High ongoing burden of cryptococcal disease in Africa despite antiretroviral roll out
Jarvis, JN; Boulle, A; Loyse, A; Bicanic, T; Rebe, K; Williams, A; Harrison, TS; Meintjes, G
AIDS, 23(9): 1182-1183.
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The effect of HIV infection on adult meningitis in Indonesia: a prospective cohort study
Ganiem, AR; Parwati, I; Wisaksana, R; van der Zanden, A; van de Beek, D; Sturm, P; van der Ven, A; Alisjahbana, B; Brouwer, A; Kurniani, N; de Gans, J; van Crevel, R
AIDS, 23(17): 2309-2316.
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Current Opinion in Infectious Diseases
Treatment of cryptococcal meningitis in resource limited settings
Sloan, DJ; Dedicoat, MJ; Lalloo, DG
Current Opinion in Infectious Diseases, 22(5): 455-463.
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JAIDS Journal of Acquired Immune Deficiency Syndromes
The Prevalence and Clinical Course of HIV-Associated Pulmonary Cryptococcosis in Uganda
Deok-jong Yoo, S; Worodria, W; Davis, JL; Cattamanchi, A; den Boon, S; Kyeyune, R; Kisembo, H; Huang, L
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Back to Top | Article Outline

AIDS; burden; cryptococcal meningitis; cryptococcus; epidemiology; HIV

© 2009 Lippincott Williams & Wilkins, Inc.


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