Prevalence of Cryptococcal Antigen Positivity Among HIV infected
patient with CD4 cell count less than 100 of Imam Khomeini hospital
in Iran
Abstract:
Objective:
Cryptococcal meningitis is one of the leading opportunistic infections associated with human
immunodeficiency virus (HIV) infection. Despite the advent and increasingly availability of
specific treatment for cryptococcosis in resource-limited settings, the mortality rate is still high,
particularly in patients with advanced cryptococcal diseases.
Method:
This Prospective Cohort study was conducted at Imam Khomeini hospital in Tehran, Iran.Serum
cryptococcal antigen was detected using the Lateral Flow Assay (LFA) There were 86 HIVinfected patients included in this study.
Result&conclusion:
The prevalence of positive serum cryptococcal antigen was 0% (0 of 86). the prevalence of
cryptococcal infection among patients with advanced acquired immunodeficiency syndrome
(AIDS) in the Iran is very low (<3%) that screening for cryptococcal antigenemia might save lives
and be cost-effective.
Introduction:
Cryptococcal infection is the most common opportunistic fungal infection in HIV-infected
patients. It is also a leading cause of mortality among HIV-infected patients in developing
countries. Cryptococcal meningitis is one of the leading opportunistic infections associated with
human immunodeficiency virus (HIV) infection1. The worldwide burden of Cryptococcal
meningitis among persons living with HIV/acquired immunodeficiency syndrome (AIDS) was
estimated in 2009 to be 957,900 cases, with approximately 624,700 deaths annually2.
Despite the advent and increasingly availability of specific treatment for cryptococcosis in
resource-limited settings, the mortality rate is still high, particularly in patients with advanced
cryptococcal diseases. Prevention of the poor outcomes of cryptococcosis by routine screening
with serum cryptococcal antigen for early cryptococcosis and prompt treatment could be a
prac- tical approach in resource-limited settings3.
The cryptococcal antigen lateral flow assay is an immunochromatographic test system for the
qualitative or semiquantitative detection of capsular polysaccharide antigens of Cryptococcus
species complex (Cryptococcus neoformans and Cryptococcus gattii) in serum and cerebrospinal
fluid (CSF). The CrAg lateral flow assay is a prescription use laboratory assay, which can aid in
the diagnosis of cryptococcosis.
Recent studies have reported that serum cryptococcal antigen screening maybe useful among
AIDS patients with CD4 cell count less than 100cells/mm3 in areas with highly endemic for
cryptococcosis4.
There are few data from the Iran on the prevalence of cryptococcal antigenemia.
The purposes of this study were to determine the prevalence of serum cryptococcal antigen in
HIV-infected patients with CD4 cell counts less than 100, to determine the risk factors for
positive serum cryptococcal antigen, and to assess the incidence of cryptococcal disease during
6 mounth follow-up period after negative cryptococcal antigen screening.
Materials andmethods:
This Prospective Cohort study was conducted at Imam Khomeini hospital in Tehran, Iran (a
referral hospital with patients from all of regions of Iran). The study was carried out between
January and septamber 2014 and followed the patient for 6 mounth after primary test with
clinical findings.
Inclusion criteria were all HIV- infected patients who had CD4 count less than 100 and had been
screened with serum cryptococcal antigen. Exclusion criteria included having primary
prophylaxis for cryptococcosis or having past history of or current cryptococcal infection.
The data including demographic information, history of AIDS-defining illnesses, clinical
symptoms and signs, laboratory data, treatment and outcomes were collected.
Serum cryptococcal antigen was detected using the Lateral Flow Assay (LFA) test .The CrAg
Lateral Flow Assay (LFA) is a dipstick sandwich immunochromatographic assay. For the
qualitative procedure, specimens are diluted 1:2 in Specimen Diluent and analyzed (Figure 1) 5.
Figure 1. CrAg Lateral Flow Assay Qualitative Procedure5
Results:
There were 86 HIV-infected patients included in this study. The mean age was 35.6 (9-56) years
and 74.4% were male. 17.4% (15 of 86) had opportunistic infection at time of collecting of
serum sample. The mean CD4 count was 45 (5-100)
The prevalence of positive serum cryptococcal antigen was 0% (0 of 86).
None of the patients (0%) with negative serum cryptococcal antigen had developed
cryptococcal meningitis after 6 mounth follow up.
Discussion:
Results from this study indicated a 0% prevalence of cryptococcal antigenemia in advanced
AIDS patients. Existing prevalence data for CrAg antigenemia are mostly from resource-limited
settings and range from as low as 2% in northern Vietnam to 21% in Benin City, Nigeria6.
The 2009 US Department of Health and Human Services guidelines for managing opportunistic
infections unequivocally state that because the incidence of cryptococcal disease is low, routine
testing of asymptomatic people for serum cryptococcal antigen is not recommended and nor is
primary prophylaxis recommended in the United States7. But in recent study The prevalence of
cryptococcal infection among patients with AIDS in the United States was 2.9% that is high
enough that screening for cryptococcal antigenemia might be cost-effective6.
One study showed that 3% prevalence of cryptococcal antigenemia is the breakpoint at which
the point at which the cost of treating Cryptococcal meningitis with amphotericin B is greater
than the cost of screening. This means that cryptococcal screening is likely to be cost-effective
in populations where the prevalence of antigenemia is greater than 3%8.
Figure2: Cost of serum cryptococcal antigen (CRAG) screening based on asymptomatic
prevalence8.
Serum cryptococcal antigen screening has an important role for the early diagnosis of
cryptococcal infection in HIV-infected patients with low CD4 cellcounts, particularly in those
with CD4 cellcount of <100 cells/mm33. This study showed the prevalence of cryptococcal
infection among patients with advanced acquired immunodeficiency syndrome (AIDS) in the
Iran is very low (<3%) that screening for cryptococcal antigenemia might save lives and be costeffective.
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