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
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: Bpark1@cdc.gov
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.
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.
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 , 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 , and, in another , we used a national surveillance report , and in the third , we used the 2007 United Nations Programme on HIV/AIDS (UNAIDS) estimate . We excluded the other two population-based studies [10,27], because we were unable to determine the HIV population.
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.
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 . 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)Image Tools
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.
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%.
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).
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) .
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) .
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 .
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 , 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 , 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 . 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 , 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.
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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Infection and ImmunityAltered Immune Response Differentially Enhances Susceptibility to Cryptococcus neoformans and Cryptococcus gattii Infection in Mice Expressing the HIV-1 TransgeneInfection and Immunity
Journal of NeurovirologyNeurovirulence of Cryptococcus neoformans determined by time course of capsule accumulation and total volume of capsule in the brainJournal of Neurovirology
Plos OneA Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, MalawiPlos One
Brazilian Journal of Infectious DiseasesStrategies to reduce mortality and morbidity due to AIDS-related cryptococcal meningitis in Latin AmericaBrazilian Journal of Infectious Diseases
Journal of InfectionThe prevalence of cryptococcal antigenemia in newly diagnosed HIV patients in a Southwest London cohortJournal of Infection
Current Medical Research and OpinionFungal diagnosis: how do we do it and can we do better?Current Medical Research and Opinion
MetallomicsA copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformansMetallomics
MycologiaEvolution of fungal sexual reproductionMycologia
MbioFungal Virulence in a Lepidopteran Model Is an Emergent Property with Deterministic FeaturesMbio
MbioMacrophage M1/M2 Polarization Dynamically Adapts to Changes in Cytokine Microenvironments in Cryptococcus neoformans InfectionMbio
Plos OneClinical Utility of the Cryptococcal Antigen Lateral Flow Assay in a Diagnostic Mycology LaboratoryPlos One
New England Journal of MedicineCombination Antifungal Therapy for Cryptococcal MeningitisNew England Journal of Medicine
New England Journal of MedicineEfficiently Killing a Sugar-Coated YeastNew England Journal of Medicine
Eukaryotic CellCryptococcus neoformans Phosphoinositide-Dependent Kinase 1 (PDK1) Ortholog Is Required for Stress Tolerance and Survival in Murine PhagocytesEukaryotic Cell
Eukaryotic CellRole of Cryptococcus neoformans Rho1 GTPases in the PKC1 Signaling Pathway in Response to Thermal StressEukaryotic Cell
Plos OneEpidemiology of Cryptococcal Meningitis in the US: 1997-2009Plos One
Japanese Journal of Infectious Diseases
Determination of Epidemiology of Clinically Isolated Cryptococcus neoformans Strains in Japan by Multi locus Sequence Typing
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Biochemical and Biophysical Research Communications3-Bromopyruvate: A novel antifungal agent against the human pathogen Cryptococcus neoformansBiochemical and Biophysical Research Communications
Journal of the Brazilian Chemical Society2D Chemometric Studies of a Series of Azole Derivatives Active against Fluconazole-Resistant Cryptococcus gattiiJournal of the Brazilian Chemical Society
Journal of ImmunologyIL-33 Signaling Regulates Innate and Adaptive Immunity to Cryptococcus neoformansJournal of Immunology
Mucosal ImmunologyT1/ST2 promotes T helper 2 cell activation and polyfunctionality in bronchopulmonary mycosisMucosal Immunology
Plos OneEvidence for Mitotic Recombination within the Basidia of a Hybrid Cross of Cryptococcus neoformansPlos One
Analytical and Bioanalytical ChemistryA high-throughput screening assay for assessing the viability of Cryptococcus neoformans under nutrient starvation conditionsAnalytical and Bioanalytical Chemistry
Future MicrobiologyRadioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cellsFuture Microbiology
Cellular MicrobiologyCryptococcus interactions with macrophages: evasion and manipulation of the phagosome by a fungal pathogenCellular Microbiology
Plos OneHigh Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in EthiopiaPlos One
Postgraduate Medical JournalPredictors of outcome in routine care for Cryptococcal meningitis in Western Kenya: lessons for HIV outpatient care in resource-limited settingsPostgraduate Medical Journal
Plos OneLong Term 5-Year Survival of Persons with Cryptococcal Meningitis or Asymptomatic Subclinical Antigenemia in UgandaPlos One
Trends in MicrobiologyCan host receptors for fungi be targeted for treatment of fungal infections?Trends in Microbiology
Clinical Infectious DiseasesRapidly Progressive Skin Lesions Requiring Admission in a Young, HIV-Infected ManClinical Infectious Diseases
Plos BiologyUnisexual and Heterosexual Meiotic Reproduction Generate Aneuploidy and Phenotypic Diversity De Novo in the Yeast Cryptococcus neoformansPlos Biology
Tropical Medicine & International HealthTuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern AfricaTropical Medicine & International Health
Antimicrobial Agents and ChemotherapyLimited Activity of Miltefosine in Murine Models of Cryptococcal Meningoencephalitis and Disseminated CryptococcosisAntimicrobial Agents and Chemotherapy
Biochemical Society TransactionsMechanisms of microbial escape from phagocyte killingBiochemical Society Transactions
Antimicrobial Agents and ChemotherapyPharmacokinetics and Pharmacodynamics of Fluconazole for Cryptococcal Meningoencephalitis: Implications for Antifungal Therapy and In Vitro Susceptibility BreakpointsAntimicrobial Agents and Chemotherapy
Journal of Biological ChemistryUnusual Galactofuranose Modification of a Capsule Polysaccharide in the Pathogenic Yeast Cryptococcus neoformansJournal of Biological Chemistry
Future MicrobiologyExserohilum rostratum fungal meningitis associated with methylprednisolone injectionsFuture Microbiology
Trends in MicrobiologyAn encapsulation of iron homeostasis and virulence in Cryptococcus neoformansTrends in Microbiology
Plos OneCryptococcus gattii Induces a Cytokine Pattern That Is Distinct from Other Cryptococcal SpeciesPlos One
DrugsCryptococcal Infections: Changing Epidemiology and Implications for TherapyDrugs
MbioCryptococcus neoformans Rim101 Is Associated with Cell Wall Remodeling and Evasion of the Host Immune ResponsesMbio
Molecular MicrobiologyUncoupling of mRNA synthesis and degradation impairs adaptation to host temperature in Cryptococcus neoformansMolecular Microbiology
International Journal of Antimicrobial AgentsEvaluation of the anticryptococcal activity of the antibiotic polymyxin B in vitro and in vivoInternational Journal of Antimicrobial Agents
Tropical Medicine & International HealthThe impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in KenyaTropical Medicine & International Health
African Health SciencesChallenges in diagnosis and management of Cryptococcal immune reconstitution inflammatory syndrome (IRIS) in resource limited settingsAfrican Health Sciences
Clinical and Vaccine ImmunologySerotype Sensitivity of a Lateral Flow Immunoassay for Cryptococcal AntigenClinical and Vaccine Immunology
Journal of ImmunologyScavenger Receptor A Modulates the Immune Response to Pulmonary Cryptococcus neoformans InfectionJournal of Immunology
Plos OneGlobal Transcriptome Profile of Cryptococcus neoformans during Exposure to Hydrogen Peroxide Induced Oxidative StressPlos One
G3-Genes Genomes GeneticsCalcineurin Governs Thermotolerance and Virulence of Cryptococcus gattiiG3-Genes Genomes Genetics
Plos OneRisk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South AfricaPlos One
Arhiv Za Higijenu Rada I ToksikologijuTwo Rare Cases of Central Nervous System Opportunistic MycosesArhiv Za Higijenu Rada I Toksikologiju
Plos OnePrevalence of Cryptococcal Antigenemia and Cost-Effectiveness of a Cryptococcal Antigen Screening Program - VietnamPlos One
Clinical Infectious DiseasesReconsidering Cryptococcal Antigen Screening in the US Among Persons With CD4 < 100 cells/mcLClinical Infectious Diseases
Current Opinion in MicrobiologyProgress in understanding fungal pathogenesisCurrent Opinion in Microbiology
Current Opinion in MicrobiologyVesicular mechanisms of traffic of fungal molecules to the extracellular spaceCurrent Opinion in Microbiology
Tropical Medicine & International HealthCryptococcal antigen prevalence in HIV-infected Tanzanians: a cross-sectional study and evaluation of a point-of-care lateral flow assayTropical Medicine & International Health
Clinical Infectious DiseasesEarly Versus Delayed Antiretroviral Therapy and Cerebrospinal Fluid Fungal Clearance in Adults With HIV and Cryptococcal MeningitisClinical Infectious Diseases
Journal of Infectious DiseasesThe Mannoprotein Cig1 Supports Iron Acquisition From Heme and Virulence in the Pathogenic Fungus Cryptococcus neoformansJournal of Infectious Diseases
European Journal of Clinical Microbiology & Infectious DiseasesAntifolates inhibit Cryptococcus biofilms and enhance susceptibility of planktonic cells to amphotericin BEuropean Journal of Clinical Microbiology & Infectious Diseases
Plos PathogensEmerging Infectious Diseases: Threats to Human Health and Global StabilityPlos Pathogens
Plos PathogensBrain Inositol Is a Novel Stimulator for Promoting Cryptococcus Penetration of the Blood-Brain BarrierPlos Pathogens
Journal of Infectious DiseasesPharmacodynamics of Liposomal Amphotericin B and Flucytosine for Cryptococcal Meningoencephalitis: Safe and Effective Regimens for Immunocompromised PatientsJournal of Infectious Diseases
Science Translational MedicineHidden Killers: Human Fungal InfectionsScience Translational Medicine
BiomedicaCryptococcosis in Colombia: Results of the national surveillance program for the years 2006-2010Biomedica
G3-Genes Genomes GeneticsComparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene Associated With Carbon Utilization and VirulenceG3-Genes Genomes Genetics
Journal of Infectious DiseasesAdvancing Translational Immunology in HIV-Associated Cryptococcal MeningitisJournal of Infectious Diseases
Journal of Infectious DiseasesThe Phenotype of the Cryptococcus-Specific CD4(+) Memory T-Cell Response Is Associated With Disease Severity and Outcome in HIV-Associated Cryptococcal MeningitisJournal of Infectious Diseases
Molecular MicrobiologyAllergen1 regulates polysaccharide structure in Cryptococcus neoformansMolecular Microbiology
Plos OnePredictors of Mortality and Differences in Clinical Features among Patients with Cryptococcosis According to Immune StatusPlos One
Journal of Infectious DiseasesCryptococcosis-IRIS is Associated With Lower Cryptococcus-specific IFN-gamma Responses Before Antiretroviral Therapy but Not Higher T-Cell Responses During TherapyJournal of Infectious Diseases
Plos OneCost Effectiveness of Cryptococcal Antigen Screening as a Strategy to Prevent HIV-Associated Cryptococcal Meningitis in South AfricaPlos One
Infection and ImmunityCryptococcus neoformans Promotes Its Transmigration into the Central Nervous System by Inducing Molecular and Cellular Changes in Brain Endothelial CellsInfection and Immunity
Molecular MicrobiologyA defect in ATP-citrate lyase links acetyl-CoA production, virulence factor elaboration and virulence in Cryptococcus neoformansMolecular Microbiology
Infection and ImmunityCongenic Strains for Genetic Analysis of Virulence Traits in Cryptococcus gattiiInfection and Immunity
Infection and ImmunityCongenic Strains of the Filamentous Form of Cryptococcus neoformans for Studies of Fungal Morphogenesis and VirulenceInfection and Immunity
Applied and Environmental MicrobiologySusceptibility of Intact Germinating Arabidopsis thaliana to Human Fungal Pathogens Cryptococcus neoformans and C. gattiiApplied and Environmental Microbiology
Journal of Infectious DiseasesMethamphetamine Alters Blood Brain Barrier Protein Expression in Mice, Facilitating Central Nervous System Infection by Neurotropic Cryptococcus neoformansJournal of Infectious Diseases
Infection and ImmunityRequirement and Redundancy of the Src Family Kinases Fyn and Lyn in Perforin-Dependent Killing of Cryptococcus neoformans by NK CellsInfection and Immunity
Current Opinion in Infectious DiseasesTreatment of cryptococcal meningitis in resource limited settingsCurrent Opinion in Infectious Diseases
JAIDS Journal of Acquired Immune Deficiency SyndromesThe Prevalence and Clinical Course of HIV-Associated Pulmonary Cryptococcosis in UgandaJAIDS Journal of Acquired Immune Deficiency Syndromes
AIDS; burden; cryptococcal meningitis; cryptococcus; epidemiology; HIV
© 2009 Lippincott Williams & Wilkins, Inc.
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