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Guo et al. Diagnosis and treatment of cryptococcal meningitis

quickly by using gold-conjugated anti-cryptococcal the synthesis of fungal DNA. Single drug treatment
[30]
monoclonal antibodies directed at C. neoformans. It is easy to produce drug resistance. 5-FC is usually
has higher sensitivity than LA and EIAs, and it is more used incombination with AmB and is superior to the
[39]
sensitive for detecting the lower antigen in CSF. [22,30] combination of AmB and FCZ. The reason is that AmB
The CrAg LFA which is low cost can be carried out at has the ability to make the cell membrane permeability
room temperature without refrigeration or complicate to increase, thus 5-FC is more susceptible to enter the
experimental equipment, takes just 10 min to get the fungus and appear synergistic fungicidal effect. Without
results. Therefore, it is expected to reform the diagnosis use of 5-FC in induction therapy will lead to increased
[40]
of cryptcoccosis in the restricted area. [36] mortality, treatment failure or recurrence. [41]
Recently, molecular biological detection comprised FCZ is one of the triazole antifungal agents and its
of chromosome pulse electrophoresis, nucleic acid mechanism of action is to destroy the cell membrane
probe, DNA fingerprinting technique and polymerase and promotes cell death by inhibiting the activity
chain reaction (PCR) has been carried out in some of cytochrome P450 by inhibiting the synthesis of
[42]
laboratories. PCR are often used at present. PCR ergosterol in fungal cell membrane. FCZ is easy
which applicates specific primer aimed at conservative to go through the blood brain barrier (BBB) to reach
sequence of C. neoformans to the detection of fungi a high concentration in CSF. However, it belongs to
[31]
is rapidly and pecifically. The primer used for multi- fungistat that the effect of killing Cryptococcus is
locus sequence typing of C. neoformans includes weaker than that of AmB. Therefore, it can be used for
CAP59, GPD1, IGS1, LAC1, PLB1, SOD1, URA5. sequential therapy after induction therapy. New drugs
[37]
The pathogenic fungi are identified as C. neoformans such as voriconazole and posaconazole have obvious
var. grubii, C. neoformans var. neoformans and hybrid anti-Cryptococcus activity in vitro.
strains by PCR. However, the requirements for the
experimental technique of PCR is so high that this kind Fractional treatment of the CM is recommended at
of test is not widely carried out in clinical practice at present, consists of AmB plus 5-FC induction therapy,
[43]
present. [31] FCZ consolidation and maintenance therapy.
Expert consensus of the diagnose and treatment
TREATMENT OF CRYPTOCOCCAL of cryptococcal infection in China recommended
MENINGITIS combination therapy with AmB 0.5-1 mg/kg per day
and 5-FC 100 mg/kg per day as induction treatment for
Cryptococcal meningitis without treatment is fatal in non-HIV associated patients which earned widespread
most cases. It is critical to diagnose early and treat approval from experts. The induction phase lasts
[44]
promptly for the improvement of survival. [38] at least 8 weeks which is different from the project of
Infectious Diseases Society of America (IDSA), and this
Antifungal agents therapy may be related to the use of the method in our country,
Antifungal drugs used commonly include namely it takes a period of time to begin with small dose
amphotericin B (AmB), 5-Flurocytosine (5-FC) and to effective maintenance dose gradually. However,
fluconazole (FCZ). large-scale clinical trials are needed to demonstrate
their validity. Then followed by consolidation therapy
AmB is a broad-spectrum antifungal agent. The with FCZ or itraconazole 200-400 mg/day at least
mechanism of AmB is to combine with fungal 12 weeks, and maintenance therapy has not been
[24]
cells membrane of ergosterol and interfere with mentioned in the Consensus [Table 1].
cell metabolism and increase the cell membrane
permeability aimed to bring about cell death. AmB is At present, there is a difference in the treatment of
the first choice for the treatment of CM, and it has the non-HIV associated patients, and its management
best early fungicidal activity (EFA). is based on the characteristics other host and the
pathogen. As a result of about 25% of the transplant
5-FC is a pyrimidine analogues, and its mechanism patients are with renal dysfunction in the diagnosis of
of action is to inhibit cell division by interfering with cryptococcal meningitis, liposome amphotericin B
[11]
Table 1: Antifungal therapeutic schedule for non-HIV associated CM patients
Schedule Course
Induction period AmB 0.5-1 mg/kg per day + 5-FC 100 mg/kg per day ≥ 8 weeks
Consolidation period FCZ/Itraconazole 200-400 mg/day ≥ 12 weeks
Maintenance period Not mentioned
HIV: human immunodeficiency virus; CM: cryptococcal meningitis; AmB: amphotericin B; 5-FC: 5-Flurocytosine; FCZ: fluconazole
252 Neuroimmunology and Neuroinflammation ¦ Volume 3 ¦ November 18, 2016