Lateral Flow Assay for Cryptococcal Antigen: An Important Advance to Improve the Continuum of Hiv Care and Reduce Cryptococcal Meningitis-Related Mortality

Vidal, José E.; Boulware, David R.

doi:10.1590/s0036-46652015000700008

Cited by 89 publications

(80 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…S5) . This observation may be relevant for diagnosticians interested in detecting cryptococcal infection prior to dissemination in at-risk patient populations, as early diagnosis of cryptococcosis greatly improves outcomes (48).…”

Section: Resultsmentioning

confidence: 99%

Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system

Denham

Verma

Reynolds

et al. 2017

Preprint

View full text Add to dashboard Cite

47Cryptococcus neoformans is a common environmental yeast and opportunistic 48 pathogen responsible for 15% of AIDS-related deaths worldwide. Mortality primarily 49 results from meningoencephalitis, which occurs when fungal cells disseminate from the 50 initial pulmonary infection site and spread to the brain. A key C. neoformans virulence 51 trait is the polysaccharide capsule. Capsule shields C. neoformans from immune-52 mediated recognition and destruction. The main capsule component, 53 glucuronoxylomannan (GXM), is found both attached to the cell surface and free in the 54 extracellular space (as exo-GXM). Exo-GXM accumulates in patient serum and 55 cerebrospinal fluid at µg/mL concentrations, has well-documented immunosuppressive 56properties, and correlates with poor patient outcomes. However, it is poorly understood 57 whether exo-GXM release is regulated or the result of shedding during normal capsule 58 turnover. We demonstrate that exo-GXM release is regulated by environmental cues 59 and inversely correlates with surface capsule levels. We identified genes specifically 60 involved in exo-GXM release that do not alter surface capsule thickness. The first 61 mutant, liv7D, released less GXM than wild-type cells when capsule is not induced. The 62 second mutant, cnag_00658∆, released more exo-GXM under capsule-inducing 63 conditions. Exo-GXM release observed in vitro correlated with polystyrene adherence, 64 virulence, and fungal burden during murine infection. Additionally, we find that exo-GXM 65 reduces cell size and capsule thickness in capsule-inducing conditions, potentially 66 influencing dissemination. Finally, we demonstrated that exo-GXM prevents immune 67 cell infiltration into the brain during disseminated infection and highly inflammatory 68 . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/186668 doi: bioRxiv preprint first posted online Sep. 10, 2017; 3 intracranial infection. Our data suggest that exo-GXM performs a different role from 69 capsule GXM during infection, altering cell size and suppressing inflammation. 70 71 Importance: 72Cryptococcus neoformans is a leading cause of life-threatening 73 meningoencephalitis in humans. C. neoformans cells produce an immunosuppressive 74 polysaccharide, glucuronoxylomannan (GXM), that is the main component of a 75 protective surface capsule. GXM is also released free into extracellular space as exo-76 GXM, although the distinction between cell-attached GXM and exo-GXM has been 77 unclear. Exo-GXM influences the outcome of infection, is the basis for current 78 diagnostic tools, and has potential therapeutic applications. This study increases our 79 basic understanding of the fungal biology that regulates polysaccharide release, 80suggesting that the release of cell-attached GXM and exo-GXM are distinctly regulated. 81

show abstract

Section: Resultsmentioning

confidence: 99%

Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system

Denham

Verma

Reynolds

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…The diagnostic use of cryptococcal capsular polysaccharide antigen (CrAg) in serum is advisable 5 this allows life-saving antifungal therapy to be initiated. In low resource settings, this test is not readily available due to cost implications.…”

Section: Discussionmentioning

confidence: 99%

Cryptococcal Meningitis in Pregnancy, the Neglected Diagnosis: A Case Report

Ngwenya¹

2016

Gynecol Obstet Res Open J

View full text Add to dashboard Cite

Introduction:Cryptococcal meningitis is an opportunistic infection of human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) that can cause maternal and fetal mortality and morbidity. This case report aims to help clinicians to consider it as a differential diagnosis in HIV-seropositive pregnant women presenting with vague symptoms. This is particularly important as HIV/AIDS is now a global pandemic. There is a test available for disease surveillance. Case Report: A 31-year-old P3 G4 HIV seropositive patient on antiretroviral therapy/cotrimoxazole presented at 29 weeks gestation by dates complaining of draining clear fluid per vagina for 24 hours, slight frontal headache and vomiting. On admission, she was ill-looking but was apyrexial with a body temperature of 36.2 °C. A sterile speculum examination confirmed ruptured membranes with a pool of liquor in the posterior vaginal fornix. She was treated as a case of preterm pre-labour rupture of membranes. Therapy consisted of erythromycin and dexamethasone. She complained of increasing frontal headaches and vomiting and on detailed examination was found to be now having neck stiffness. A lumbar puncture was performed and microscopy showed Cryptococcus neoformans. She was managed by a multidisciplinary team involving physicians and was treated with antifungals. She delivered prematurely by normal vaginal delivery a baby boy weighing 2100 g with Apgar 7 and 9 scores at 1 and 5 minutes respectively. Post-partum she continued to fit for a day but subsequently the convulsions stopped and the patient began to improve clinically. Conclusion: There is need to raise awareness amongst clinicians about serious opportunistic infections in HIV infected pregnant mothers for early diagnosis and treatment. Antifungal therapy can be life-saving and prevent maternal deaths.

show abstract

“…The CrAg lateral flow assay (LFA) is the most sensitive and specific method for detecting early disseminated infection (14, 15), and is the preferred first-line recommended test for diagnosis (16, 17). Persons presenting with a CD4 count <100 cells/μl have the highest benefit from screening and treatment (18).…”

Section: Screening Asymptomatic Patients At Risk For Meningitismentioning

confidence: 99%

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

Lofgren

Abassi

Rhein

et al. 2017

Expert Review of Anti-infective Therapy

View full text Add to dashboard Cite

Introduction Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert Commentary Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

show abstract

Lateral Flow Assay for Cryptococcal Antigen: An Important Advance to Improve the Continuum of Hiv Care and Reduce Cryptococcal Meningitis-Related Mortality

Cited by 89 publications

References 52 publications

Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system

Regulated release of cryptococcal polysaccharide drives virulence and suppresses immune cell infiltration into the central nervous system

Cryptococcal Meningitis in Pregnancy, the Neglected Diagnosis: A Case Report

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

Contact Info

Product

Resources

About