World Journal of AIDS, 2011, 1, 8-14
doi: 10.4236/wja.2011.11002 Published Online March 2011 (http://www.SciRP.org/journal/wja)
1
Associated Factors for In-Hospital Mortality in
Patients with Meningeal Cryptococcosis and HIV
Infection at a Local Hospital in Lima, Peru
Canessa J.C.1, Cabrera D.1, Eskenazi J.1, Samalvides F1
1Cayetano He re dia University, Lima, Peru.
Received March 8th, 2011; revised March 17th, 2011; accepted March 18th, 2011.
ABSTRACT
Objective: To determine the associated factors for in-hospital mortality in patients with meningeal cryptococcosis and
HIV infection at a local hospital in Lima, Peru Materials and me thods: We carried out a case-control study by reviewing
the medical histories available at a local hospital in Lima, Peru. We determined the factors associated with mortality
using a logistic regression model. Results: The information of 90 patients was analyzed, 37 dead and 53 alive. In the
multivariate analysis we found two variables associated with mortality: Glasgow at a dmission (OR = 4. 55 (1.61 – 12.20),
p = 0.01) and serum antigen titer greater than 1024 (OR = 20.48 (1.6 – 261.04, p = 0.02). The protective factor found was
a longer hospita lization sta y (OR = 0.80 (0.69 – 0.93, p = 0.005).Conclusions: A low Glasgow sco r e and serum antig en
titer greater than 1024 are associated factors with mortality, whereas hospitalization length is a protective factor.
Keywords: Meningeal Cryptococcosis, Cryptococcus, HIV, Mortality, Death, Cryptococcal Meningitis
1. Introduction
Cryptococcosis is an opportunistic disease [1] which is
potentially mortal [2,3], caused by the encapsulated cos-
mopolitan fungus Cryptococcus neoformans [4,5], of
which three variants exist: neoformans, grubii (most
prevalent worldwide) [4,6,7] and gatti [8,9]. Its pato-
genicity is related to patients with altered T-cell immunity
[8,10], particularly those affected with the Human Im-
munodeficiency Virus (HIV) and with CD4 blood counts
below 100/m m3 [5,8]. Cryptococcosis defines AIDS in up
to 25% of cases [11,12].
This patho gen is foun d in pigeon droppings [4,5] and i n
the heartwood of eucalyptus trees in tropical and sub-
tropical areas[5,7,13]. It most often enters the host
through inhalation [7,8], forming a primary infection in
immunocompetent patients [8]. In those immunocom-
promised, it travels hematogenously with a predilection
for the central nervous system [8], causing an acute or
subacute meningoencephalitis [14]. The probability of
acquiring cryptococc osis in HIV-infected patients wh o are
not under HAART (Highly Active Anti-Retroviral Ther-
apy) is around 10-30 % [12,15], with an annual incid ence
in Latin- American series of 1.1-3.7 per m illion inha bitants
per year [12].
The most common signs and symptoms are: headache,
fever [7,10,16], vomiting [15,16], cranial nerve palsy
[7,8], altered consciousness [10], convulsions [8], visual
alterations [7,15,17], dermatological lesions [10], but
only one third of patients will present classic meningeal
signs [16]. The natural history of the di sease shows a 3 5%
survival at day 14 and 0% survival at day 42 [3] .
Factors that have been associated to mortality at ad-
mission are: cryptococcemia [1,18], absence of treatment
with HAART [19], abnormal mental status [8,11,19],
CD4 values below 5 0/mm3 [20], intrac ranial hype rtension
[10,11], malnutrition [19], hyponatremia [21], lumbar
puncture’s opening pressure greater than 25cmH2O
[7,22,23], high antigen titer [7,10,23], low cerebrospinal
fluid (CSF) inflammatory response [7,21,23], and an
abnormal cerebral image (magnetic resonance or com-
puted tomography) [10].
Mortality since the extended use of HAART has de-
creased [25-29], although the mortality in the acute phase
is still around 10-20% [30,31]. In countries in South
America, Africa and Asia, the use of HAART is still low
[12,25,32,33]. On the other hand, prognosis is still poor in
patients receiving antifungal m onotherapy, with a 60-65%

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and 9HIV Infection at a Local Hospital in Lima, Peru
failure at week ten [10,34]. Besides, because of its high
toxicity the treatment itself has been related to death,
especially in the absence of an adequate c oncom itant flui d
therapy [19]. It is important to mention that in some Af-
rican countries , meningeal cryptococcosis mortality is
even higher than that caused by tuberculosis [28].
The aim of this study is to determine the associated
factors for in-hospital mortality in patients with meningeal
cryptococcosis and HIV-infection at a hospital in Li-
ma-Peru because of the nonexistence of previous studies
of this sort in our country.
2. Materials and Methods
2.1. Study Design
We carried out an observational, longitudinal case-control
study, in patients with meningeal cryptococcosis and
HIV-infection treated at a local hospital in Lima, Peru
between January 1st 2000 and December 31st 2009. We
included as cases, patients who died during hospitaliza-
tion, with a confirmed diagnosis of HIV-infection [8,26],
and of meningeal cryptococcosis by either CSF cultures,
positive serum an tigen titers or a positive CSF In dian Ink,
and symptoms compatible with meningoencephalitis
[8,13]. In the controls, we included patients who survived
the hospitalization, and who had an equally confirmed
diagnosis of both HIV-infection and meningeal crypto-
coccosis. We excluded from both branches of the study
patients without a confirmed diagnosis of meningeal
cryptococcosis, those immunocompromised by others
causes rather than HIV, those who received antifungal
treatment within one week previous to admission, or
those with contraindications to a lumbar puncture. In
recurrent patients, only the first hospitalizatio n was taken
into account.
2.2. Gathering of Information
We revised both medical records and epicrisis, to obtain
the following information: past medical history [24,35],
clinical, laboratory and mycological findings [26] and
CSF characteristics (initial opening pressure, cellularity,
cytochemical analysis, Indian Ink and fungal culture
[2,26]. Finally, we registered total hospitalization dura-
tion and the outcome.
2.3. Statistical Analysis
Sample size was calculated using EpiInfo v6.1, with a
1:2 ratio (cases:controls), a statistic significance of 95%
and a statistical power of 80% [18]. Considering expo-
sure percentages among an opening pressure greater than
25cmH2O, we obtained a required sample size of 10:20
(OR = 20.4) [23], while in the case of serum antigen titer
greater than 1/1024, we obtained a sample size of 27:54
(OR = 3.17) [36]. Qualitative variables were analyzed
using chi-squared and Fisher, while quantitative variables
used t-student distribution and U-Mann-Whitney, all of
them with a significance level of 0.05. Afterwards, we
carried out a multiple logistic regression. We obtained
the consent of the ethical department of both Cayetano
Heredia University and Cayetano Heredia Hospital.
3. Results
A total of 90 patients were included i n t he study (3 3 ca ses
and 57 controls). The range of age varied between 20 and
74 years, with a m ean value of 35 (sd 10.31) years in those
who died and 34.7 (sd 10.04) in those who survived.
76.67% of patients were male. As past medical history,
16.25% received HAART before admission (12 of which
survived, while only 1 who died). We found a mean time
between HIV diagnosis and hospital admission of 6
months in the cases versus 14 months in the controls (p =
0.025).
Hospitalization stay was of 7 days on average in pa-
tients wh o die d, com pared to 21 days i n thos e who di d not
die (p = 0.0001). Mean arterial pressure was of
111.77/70.34 mmHg, with differences between cases and
controls of 119.72/75.84 and 107.8/67.6 respectively (p =
0.0007 in the systolic and p = 0.0005 in the diastolic).
Furthermore, the body mass index (BMI) was on average
20.62 kg/m2. In the neurological examination, the mean
Glasgow score was 14.4, with values of 13.29 in those
who died, contrasted with 14.84 in t hose who did not (p <
0.001). The presence of focalization in the cases was 37%
(n = 10) while in the controls it was 3.7% (n = 2).
In laboratory studies, we observe that the mean value
for CD4 in patients who died was 14/mm3, compared to a
value of 36/mm3 in those who survived (p = 0.04), while
in the case of albumin, the mean in this study was of 3.14
g/dL (2.7 g/dL in the former group and 3.52 g/dL in the
latter, p = 0.039).
Finally, median serum antigen titer was 1/4096 in the
cases, while in the controls it was 1/256 (p = 0.0001).
Referring to CSF characteristics, we found a mean ini-
tial opening pressure of 30.94 cmH2O (35.91 in the dead
versus 26. 67 in those who s urvived, p = 0.1 2), white blood
cell count was on average 38.62, while glucose and pro-
teins scored 36.63 and 76.9 mg/dL, respectively. The
remaining results can be consulted in Table 1.
In the logistic regression, the protective factor was
hospitalization duration, with an odds ratio of 0.80 (p =
0.005) in the multiv ariate an alysis. On the other h and, th e
associated factors to in-hospital mortality in the univariate
analysis were: blood pressure (OR = 1.07, p = 0.004 and
OR = 1.10, p = 0.003) in the case of systo lic and diasto lic

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and
HIV Infection at a Local Hospital in Lima, Peru
10
Table 1. Statistical tests of the variables.
Patients with HIV and meningeal cryptococcosis
Variable Died Survived Test p-value
Time of HIV di agnosis (in months) 6 (1 - 24) 14 (3 - 60) U-Mann-Whitney 0.025
HAART treatment Fisher 0.095
Yes 1 12 Chi-squared 0.055
No 23 44
Previous episode of meningeal
cryptococcosis Chi-squared 0.11
Yes 5 6
No 13 44
Oportunistic diseases Chi-squared 0.14
Yes 24 37
Previous medical
history
No 6 20
Age (in years) 35 sd 10.31 34.7 sd 10.04 t-student 0.89
Gender Chi-squared 0.23
Female 10 11
Male 23 46
Hospitalization duration (in days) 7 (5 - 13) 21 (17.5 - 33.5) U-Mann-Whitney 0.0001
Weight (in kilograms) 54.87 sd 8.36 57.13 sd 9.25 t-student 0.44
Clinical
characteristics
Height (in meters) 1.56 sd 0.02 1.63 sd 0.07 t-student 0.07
BMI (kg/m2) 19.55 sd 3.26 20.95 sd 3.84 t-student 0.47
Blood pressure (mmHg)
Systolic 119.72 sd 20.27 107.8 sd 9.04 t-student 0.0007
Diastolic 75.84 sd 12.08 67.6 sd 7.43 t-student 0.0005
Pulse (per minute) 82.36 sd 14.56 84.26 sd12.86 t-student 0.56
Respiratory frequency (per minute) 22 sd 6.1 20.36 sd 3.04 t-student 0.12
Temperature (in ºC) 37.03 sd 0.35 37.24 sd 0.70 t-student 0.25
Glasgow scale 13.29 sd 1.78 14.84 sd 0.66 t-student <0.001
Focalization Chi-squared <0.001
Yes 10 2 Fisher <0.001
No 17 52
Laboratory
stud
y
WBC count (/microL) 7222.48 sd 4816.4 5601.37 sd 3156.8 t-student 0.09
Hemoglobin (g/dL) 13.84 sd 8.99 10.76 sd 1.79 t-student 0.35
Serum electrolytes (in mEq/dL)
Sodium (Na+) 133.61 sd 5.61 136.29 sd 4.38 t-student 0.048
Potasium (K+) 3.98 sd 0.43 3.96 sd 0.63 t-student 0.65
Chloride (Cl-) 101.27 sd 6.35 103.57 sd 5.65 t-student 0.17
CD4 (/mm3) 14 (2 - 18) 36 ( 23 - 105) U-Mann-Whitney 0.04
Albumin (g/dL) 2.7 sd 0.24 3.52 sd 0.67 t-student 0.039
Serum antigen titer 1/4096 (1/2048 - 1/4096)1/256 (1/32 - 1/1024) U-Mann-Whitney 0.0001
Culture Chi-squared 0.24
Micologic study Positive 6 4
Negative 13 3
CSF
characteristics Opening pressure (cmH2O) 35.91 sd 16.87 26.67 sd 12.39 t-student 0.12
Leukocytes (/microL) 10 ( 3 - 20.5) 4 ( 0 - 17) U-Mann-Whitney 0.33
Proteins (mg/ d L ) 87 sd 53.81 73.08 sd 51.87 t-student 0.4
Glucose (mg/dL) 30.93 sd 20.16 38.94 sd 14.87 t-student 0.11
This table de picts t he c omplet e set of variable s ana lyze d in this s tudy, showing t he sta tistica l diffe rence betwee n patie nts who died a nd thos e who sur vived du ring
ospitalization. h

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and 11 HIV Infection at a Local Hospital in Lima, Peru
respectively, Glasgow score (OR = 3.13, p < 0.001), se-
rum antigen titer (OR = 23.13, p = 0.003) and focalization
(OR = 15.29, p = 0.001). In the multivariate analysis, the
factors that remained associated to a negative outcome
were serum antigen titers (OR = 4.55, p = 0.01) and Glas-
gow score (OR = 20.48, p = 0.02). The complete da ta for
the logistic regression model can be reviewed in Table 2.
4. Discussion
This is the first investigation carried out in Peru aiming to
find the mortality-associated factors in patients with
meningeal cryptococcosis and HIV infection, despite the
high mortality among them. The significant clinical pat-
terns were: blood pressure, serum albumin level and de-
prived mental status. Blood pressure was higher in those
patients who died, probably reflecting intracranial hy-
pertension [29], concurring with previous studies in New
Guinea [36] and Thailand [37]. Similarly, it was found
that patients presented with lower serum albumin levels in
the case group, as an indirect indication of malnutrition
and impl ying that these patient s had a worse previous state
at admission. Referring to the neurological findings, the
scores in the Glasgow scale were lower in t hose who died,
and that same patients group had focalization more often,
matching the findings of other studies [8,11,19,22] and
possibly si gnaling that t hese patient s at a dmission were i n
a poorer mental state, either because of a longer disease
evolution or because of factors inherent to the subject.
In the laboratory study, patients who died presented hy-
ponatremia more often, exhibiting an internal imbalance
and a greater systemic compromise. Subramian et al. in
2005 reported similar findings [21 ], but it is still not po s-
sible to propose a cut point below which it can be con-
sidered hazardous. In what concerns CD4 levels, those in
the cases were substantially lower than those in the con-
trols. In other studies it has been reported a global mean
CD4 value of 45/mm3 in meningeal cryptococcosis pa-
tients [12,15,24], without differentiating between those
Table 2. Univariate and multivariate logistic regression.
Category Variable OR 95% (IC) a p-value OR 95% (IC) b p-value
Time of HIV di agnosis (in months) 0.98 (0.95 - 1.004) 0.11
HAART treatment 0.087
Yes 0.15 (0.019 -1.3)
Previous medical
history
No 1
Oportunistic diseases 0.14
Yes 2.16 (0.75 - 6.16)
No 1
Hospitalization duration (in days) 0.87 (0.81 - 0.93) >0.001 0.80 (0.69 - 0.93) 0.005
Blood pressure ( in mmHg)
Systolic 1.07 (1.02 - 1.12) 0.004
Diastolic 1.10 (1.03 - 1.17) 0.003
Glasgow scale 3.13 (1.67 - 5.88) >0.001 4.55 (1.61 - 12.20) 0.01
Focalization 0.001
Yes 15.29 (3.04 - 76.81)
Clinical
characteristics
No 1
WBC count (/microL) 1.00 (0.99 - 1.00) 0.09
Serum sodium (mEq/dL) 1.14 (1.00 - 1.30) 0.055
CD4 count 1.12 (0.97 - 1.32) 0.14
Laboratory
study
Serum albumin 125 (0.37 - 10000) 0.1
Micologic study Serum antigen titer 23.13 (2.87-186.1) 0.003 20.48 (1.6 - 261.04) 0.02
This table presents the univariate (ICa) and multivariate (ICb) analysis for those variables that resulted significant in the statistical test shown in table 1.

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and 12
HIV Infection at a Local Hospital in Lima, Peru
who die and those who survive. In this study, we obtained
a much lower mean in patients who died.
Some publications state that up to 60% of patients with
meningeal cryptococcosis present with a serum antigen
titer of 1/1024 [35 ] or 1/2048 (CSF) [6,19,23], with a 90%
sensibility [8,20,38]. In our study, the cut point in the case
of the initial serum antigen was also located at 1/1024,
because above that dilution the proportion of deaths in-
creased importantly. However, the follow-up dilutions of
antigen titer do not predict th e final outcome [39,40].
In what concerns the CSF, a previous study in our
country showed that 57.9% of the initial opening pres-
sures in the lumbar puncture were abnormally high [15].
In our c ase, the m ean opening pre ssure was hi gher in th ose
who died, but without finding significant differences
between bot h groups. Opening pressures a bove 25 cmH2O
have been associated to higher short-term mortality
[7,23,35] and with a requirement for daily decompression
[19,29,41]. The fact that we did not find this associati on is
probably due to the fact that some of the records did not
contain data for this specific variable, even though the
procedure was executed. Having said that, it is described
that as many as 25% of patients with cryptococcosis can
have a normal CSF study [16,24].
In the multivariate analysis, we found as a protective
factor the duration of hospitalization, resulting that each
additional day reduced in 29% the probability of dying. In
studies in other countries, it has been reported that the
mean time of death is around 10 to 14 days [7,11,19],
while in our case it was much shorter (7 days) [23]. This
could be explained because patients in our country take
longer to seek for professional help, presenting at the
emergency department in a more debilitated neurologic
and systemic state, and dying sooner because of compli-
cations such as intracranial hypertension.
Mortality-associated factors included a low score in the
Glasgow scale and elevated serum antigen titers. In the
former, it was found that the decrease in one point in the
scale meant 4.55 times more probability of dying. In the
case of the serum antigen titers, the variable was di-
chotomized with a cut point at 1/1024. This concurs to
Dromer et al. prospective study where a 1/512 cut point
was proposed as a predictor of therapeutic failure at day
14 [10]. On another level, neurologic focalization is as-
sociated to death in the univariate regression model, but
was diluted in the multivariate study, proba bly because of
a lack of power of the study. This contrasts to publications
by Cachay et al. who were able to link focalization with
complications including death [22].
REFERENCES
[1] S. Jean, C. Fang and W. Shau, et al, “Cryptococcaemia:
clinical features and prognostic factors,” Q J Med, Vol.
95, No. 8, 2002; pp. 511- 518.
[2] V. Lakshmi, T. Sudha and V. Teja, et al, “Prevalence of
central nervous system cryptococcosis in human
immudeficiency virus reactive hospitalized patients,”
Indian Journal of Medical Science, Vol. 25, No. 2, 2007;
pp. 146-149.
[3] P. Mwaba, J. Mwansa and C. Chintu, et al, “Clinical
presentation, natural history, and cumulative death rates
of 230 adults with primary cryptococcal meningitis in
Zambian AIDS patients treated under local conditions,”
Postgraduate Medical Journal, Vol. 77, No. 941, 2001;
pp. 769-773. doi:10.1136/pmj.77.914.769
[4] B. Bustamante and D. Swinne, “Aislamiento de
Cryptococcus neoformans variedad gattii en dos pacientes
peruanos,” Revista Iberoamericana de Micologia, Vol. 15,
1998, pp. 22-24.
[5] C. Klock, M. Cerski and L. Goldani, “Histopathological
aspects of neurocryptococcosis in HIV-infected patients:
autopsy reports of 45 patients,” International Journal of
Surgical Pathology, Vol. 17, No. 6, 2009; pp. 444-448.
[6] C. Charlier, F. Dromer and C. Lévêque, et al,
“Cryptococcal neuroradiological lesions correlate with
severity during cryptococcal meningoencephalities in
HIV-positive patients in the HAART era,” PLoS Med, Vol.
3, No. 4, 2008; pp. 1-7.
[7] J. Jarvis and T. Harrison, “HIV-associated cryptococcal
me- ningitis,” AIDS, Vol. 21, No. 16, 2007; pp.
2119-2129. doi:10.1097/QAD.0b013e3282a4a64d
[8] D. Cangelosi, L. De Carolis and L. Trombetta, et al,
“Cr ipt oco cosis mení ngea asociada al SIDA. Aná lisis de los
pacientes varones HIV(+) con criptococosis meníngea
internados en la Sala 11 del Hospital Francisco J Muñiz,”
Revista de la Asociación Médica Argentina, Vol. 120, No.
3, 2007; pp. 25-30.
[9] T. Moreira, M. Ferreira and R. Marques Ribas, et al,
“Criptococose: estudio clínico-e pidemiológico, laboratorial
e das variedades do fungo em 96 pacientes,” Revista da
Sociedade Brasileira de Medicina Tropical, Vol. 39, No.
3, 2006, pp. 255-258.
doi:10.1590/S0037-86822006000300005
[10] F. Dromer, S. Mathoulin-Pélissier and O. Launay, et al,
“Determinants of disease presentation and outcome
during cryptococcosis: the crypto A/D study,” PLoS Med,
Vol. 4, No. 2, 2007; pp. 0297-0308.
[11] A. Brouwer, A. Rajanuwong and C. Wirongrong, et al,
“Combination antifungal therapies for HIV-associated
cryptococcal meningitis: a randomised trial,” Lancet, Vol.
363, No.5, 2004, pp. 1764-1767.
[12] J. Lizarazo, M. Linares and C. de Bedout, et al, “Estudio
clínico y epidemiológico de la criptococosis en Colombia:
resultados de nueve años de la encuesta nacional,”
Biomédica, Vol. 27, No. 1, 2007; pp. 94-109.
[13] A. Chakrabarti, “Epidemiology of central nervous system
mycoses,” Neurology India, Vol. 55, No. 3, 2007, pp.
191-197.doi:10.4103/0028-3886.35679

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and 13 HIV Infection at a Local Hospital in Lima, Peru
[14] L. Trombetta, G. Poustis and A. Bocassi, et al, “Líquido
cefalorraquídeo en pacientes con criptococosis asociada
al SIDA,” Acta Bioquímica Clínica Latinoamericana,
Vol. 42, No. 1, 2008; pp. 61-64.
[15] R. Andrade, “Características epidemiológico-clínicas de
un grupo de pacientes con SIDA y meningoencefalitis
criptococócica en el HNCH,” Tesis para optar por el
grado de Médico Cirujano, UPCH: Lima - Perú,2001.
[16] H. Manji and R. Miller, “The neurology of HIV
infection,” Journal of Neurology, Neurosurgery &
Psychiatry, Vol. 75, Suppl. 1, 2004; pp. i29-i35.
doi:10.1136/jnnp.2003.034348
[17] R. Thakur, S. Sarma and S. Kushwaha, “Prevalence of
HIV- associated cryptococcal meningitis and utility of
microbiological determinants for its diagnosis in a
tertiary care center,” Indian Journal of Pathology and
Microbiology, Vol. 51, No. 2, 2008; pp. 212-214.
doi:10.4103/0377-4929.41689
[18] A. Comarú, C. Bittencourt and F. de Mattos, et al,
“Cryptococcemia. An analysis of 28 cases with emphasis
on the clinical outcome and its etiologic agent,” Revista
Iberoamericana de Micologia, Vol. 21, 2004, pp. 143-146.
[19] A. Kambugu, D. Meya and J. Rhein, et al, “Outcomes of
Crypto- coccal Meningitis in Uganda before and after
the availability of highly active antiretroviral therapy,”
Clinical Infectious Diseases, 2008; Vol. 46, No. 6, pp.
1694-1701.
[20] B. Ojikutu, H. Zheng and R. Walensky, et al,
“Predictors of mortality in patients initiating
antiretroviral therapy in Durban, South Africa,” South
African Medical Journal, Vol. 98, No. 3, 2008, pp.
204-208.
[21] S. Subramanian and D. Mathai, “Clinical manifestations
and management of cryptococcal infection,” Postgraduate
Medical Journal, Vol. 51, Suppl. 1, 2005; pp. S21-S26.
[22] E. Cachay, J. Caperna and A. Sitapati, et al, “Utility of
clinical assessment, imaging, and cryptococcal antigen
titer to predict AIDS-related complicated forms of
cryptococcal meningitis,” AIDS Research and Therapy,
Vol. 7, No. 29, 2010; pp. 1-6.
[23] J. Graybill, J. Sobel, M. Saag, et al, “Diagnosis and
management of increased intracranial pressure in
patients with AIDS and cryptococcal meningitis,”
Clinical Infectious Diseases, Vol. 30, No. 1, 2000; pp.
47-54. doi:10.1086/313603
[24] C. Darras-Joly, S. Chevret, M. Wolff, et al, “Cryptococcus
neoformans infection in France: epidemiologic features of
and early prognostic parameters for 76 patients who were
infected with Human Immunodeficiency Viru s,” Clinical
Infectious Diseases, Vol. 23, No. 8, 1996; pp. 369-376.
doi:10.1093/clinids/23.2.369
[25] S. Antinori, A. Ridolfo, M. Fasan, et al, “AIDS-associated
cryptococcosis: a comparison of epidemiology, clinical
features, and outcome in the pre- and post-HAART eras.
Experience of a single centre in Italy,” HIV Medicine,
Vol. 10, 2009; pp. 6-11.
doi:10.1111/j.1468-1293.2008.00645.x
[26] S. Chottanapund, P. Singhasivanon and J. Kaewkungwal,
et al, “Survival time of HIV-infected patients with
cryptococcal meningitis,” Journal of The Medical
Association of Thailand, Vol. 90, No. 10, 2007, pp.
2104-2111.
[27] T. Lu, H. Chang and L. Chen, et al, “Changes in causes
of death and associated conditions among persons with
HIV/AIDS after the introduction of highly active
antiretroviral therapy in Taiwan,” Journal of the
Formosan Medical Association, Vol. 105, No. 7, 2006; pp.
604-609. doi:10.1016/S0929-6646(09)60158-3
[28] B. Park, K. Wannemuehler and B. Marston, et al,
“Estimation of the current global burden of cryptococcal
meningitis among persons living with HIV/AIDS,” AIDS,
Vol. 23, No. 4, 2009; pp. 525-530.
doi:10.1097/QAD.0b013e328322ffac
[29] J. Perfect, W. Dismukes and F. Dromer, et al, “Clinical
practice guidelines for the management of cryptococcal
di seas e: 2010 update by the Infectious Diseases Society of
America,” Clinical Infectious Diseases, Vol. 50, No. 1,
2010, pp. 291- 322.
[30] O. Lortholary, G. Poizat and V. Zeller, et al, “Long-term
outcome of AIDS-associated cryptococcosis in the era of
combination antiretroviral therapy,” AIDS, Vol. 20, No.
17, 2006, pp. 2183-2191.
doi:10.1097/01.aids.0000252060.80704.68
[31] J. Perfect, “Cryptococcus neoformans,” Principles and
practice of infectious diseases, Philadelphia, 2005, pp.
2997-3012.
[32] R. Sobhani, A. Basavaraj and A. Gupta, et al, “Mortality
& clinical characteristics of hospitalized adult patients
with HIV in Pune, India,” Indian Journal of Medical
Research, Vol.126, No. 8, 2007; pp. 116-121.
[33] T. Warkentien and N. Crum-Cianflone, “An update on
Cry ptococcus among HIV-infect ed patients,” International
Journal of STD & AIDS, Vol. 21, No. 10, 2010, pp.
679-684. doi:10.1258/ijsa.2010.010182
[34] P. Robinson, M. Bauer and M. Leal, et al, “Early
mycological treatment failure in AIDS-associated
cryptococcal meningitis,” Clinical Infectious Diseases,
Vol. 28, No. 1, 1999, pp. 82-92. doi:10.1086/515074
[35] U. Jongwutiwes, S. Sungkanupar ph and S. Kiertibu ranakal,
“Comparison of clinical features and survival between
cryptococcosis in Human Immunodeficiency Virus
(HIV)-positive and HIV-negative patients,” Japanese
Journal of Infectious Disease, Vol. 61, 2008, pp. 111-115.
[36] R. Seaton, S. Naraqi and J. Wembri, et al, “Predictors of
outcome in Cryptococcus neoformans var. gattii
meningitis,” Q J Med, Vol. 89, 1996, pp. 423-428.
[37] J. Fan-Harvard, P. Yamaguchi and E. Smith, et al,
“Diastolic hypertension in AIDS patients with cryptococcal
meningitis,” American Journal of Medicine, Vol. 93,
1992, pp. 347-348. doi:10.1016/0002-9343(92)90245-7
[38] P. Imwidthaya, “N P. Cryptococcosis in AIDS,”
Postgraduate Medical Journal, Vol. 76, 2000, pp. 85-88.
doi:10.1136/pmj.76.892.85

Associated Factors for In-Hospital Mortality in Patients with Meningeal Cryptococcosis and
HIV Infection at a Local Hospital in Lima, Peru
14
[39] W. Powderly, G. Cloud and W. Dismukes, “Measurment
of cryptococcal antigen in serum and cerebrospinal fluid:
value in the management of AIDS-associated cryptococcal
meningitis,” Clinical Infectious Diseases, Vol. 18, No. 5,
1992, pp. 789-792.
[40] A. Spinello, A. Radice and L. Galimberti, “The role of
cryptococcal antigen assay in diagnosis and monitoring of
cryptococc al menin gitis ,” Journal of Clinical Microbiology,
Vol. 43, No. 11, 2005, pp. 5828-5829.
[41] P. Pappas, “Managing cryptococcal meningitis is about
handling the pressure,” Clinical Infectious Diseases, Vol.
40, No. 1, 2005, pp. 480-482.