Cryptococcal Antigenemia Research Articles

Implications of Undiagnosed Subclinical Cryptococcal Meningitis in Clinically Asymptomatic Low-Titer Cryptococcal Antigenemia Among PLWH: More Questions to Answer.

Implications of Undiagnosed Subclinical Cryptococcal Meningitis in Clinically Asymptomatic Low-Titer Cryptococcal Antigenemia Among PLWH: More Questions to Answer.

Economic impact of extending reflexed cryptococcal antigenaemia CD4 threshold in South Africa.

Reflexed cryptococcal antigenaemia (CrAg) testing has been offered since 2016 in South Africa, on remnant CD4 specimens, for people with a count < 100 cells/μL. Local guidelines recommended extending testing to 200 cells/μL. This study assessed the cost per result and annual equivalent costs (AEC) for CD4 counts < 100 cells/μL and 100 to 200 cells/μL, as well as determining the cost to find one CrAg-positive case. An ingredients-based costing was used to determine the cost per result. The CrAg detection rate for < 100 cells/μL was obtained from operational reports of 2019. For 100 cells/μL to 200 cells/μL, a CrAg detection rate of 2% was assumed. One-way sensitivity analysis determined the impact of varying CrAg detection rates on the cost to find one case. Local data from the Western Cape province, which offers testing for counts of 100 cells/μL to 200 cells/μL, from September 2022 to January 2023, were interrogated to establish detection rates. There were 283 240 (AEC: $1 670 370) specimens with counts of < 100 cells/μL and 300 624 (AEC: $1 772 890) with counts of 100 cells/μL to 200 cells/μL. A cost per result of $5.897 was reported. The cost to find one CrAg case ranged from $589.74 to $73.72 for a detection rate of 1% to 8%. Local data for a count of 100 cells/μL to 200 cells/μL revealed a CrAg detection rate of 1.6%. The study findings reveal that extending reflexed CrAg testing to 200 cells/μL would double test volumes with fewer positive cases reported for those with a count of 100 cells/μL to 200 cells/μL.

Adjunctive Single-Dose Liposomal Amphotericin to Prevent Cryptococcal Meningitis in People With Human Immunodeficiency Virus (HIV)-Associated Cryptococcal Antigenemia and Low Plasma Cryptococcal Antigen (CrAg) Titers.

Cryptococcal meningitis is a leading cause of AIDS-related mortality. Cryptococcal antigen (CrAg) predicts the development of meningitis. Historically, despite standard- of-care fluconazole, 25%-30% of asymptomatic CrAg-positive persons develop breakthrough meningitis or death. We evaluated whether adding single high-dose liposomal amphotericin B to standard pre-emptive fluconazole therapy could improve meningitis-free survival. Participants with human immunodeficiency virus (HIV) and asymptomatic cryptococcal antigenemia in Uganda were randomized to liposomal amphotericin B (10 mg/kg once) with fluconazole or fluconazole alone through 24 weeks. We compared 24-week, meningitis-free survival time between treatment groups. After the second interim review, the Data Safety and Monitoring Board recommended no further enrollment of participants with low plasma CrAg lateral flow assay titers (≤1:80) due to futility. Herein, we present the results of participants with low plasma CrAg titers. 168 participants enrolled into the ACACIA trial had low plasma CrAg titers (≤1:80). During 24 weeks of follow-up, meningitis or death occurred in 14.5% (12/83) of participants randomized to liposomal amphotericin B with fluconazole versus 10.6% (9/85) assigned to fluconazole alone (hazard ratio, 1.42; 95% CI, .60-3.36; P = .431). Adverse events were more frequent in participants assigned to the intervention versus standard-of-care (28% vs 12%; P = .011). Among CrAg-positive persons with low titers (≤1:80), the addition of single-dose liposomal amphotericin B to fluconazole as pre-emptive therapy provided no additional clinical benefit. This trial provides supportive evidence that, in asymptomatic populations with low plasma CrAg titers, lumbar punctures are likely unnecessary as administration of meningitis treatment did not improve outcomes. Clinicaltrials.gov (NCT03945448).

Prevalence of Cryptococcal Antigenemia and Lateral Flow Assay Accuracy in Severely Immunosuppressed AIDS Patients.

This study aimed to estimate the prevalence of cryptococcal antigenemia detected by lateral flow assay (LFA) in AIDS patients and its accuracy in the diagnosis of cryptococcosis. Conducted at a university hospital in Brazil from March 2015 to July 2017, it included AIDS patients over 18 years old with a CD4+ count ≤ 200 cells/mm3. Cryptococcal antigen (CrAg) detection using LFA and latex agglutination (LA), along with blood and urine cultures, were performed. The reference standard was the identification of Cryptococcus spp. in clinical specimens through microbiological or histopathological examination. Among 230 patients, the prevalence of CrAg detected by LFA (CrAg LFA) was 13.0%. Factors associated with cryptococcal antigenemia included fever, vomiting, seizures, and a lack of antiretroviral therapy. The sensitivity and specificity of CrAg LFA were 83.9% and 98.0%, respectively. The positive predictive value (PPV) was 86.7%, the negative predictive value (NPV) was 97.5%, and overall accuracy was 96.1%. Cross-reactions were observed in patients with histoplasmosis and paracoccidioidmycosis, but not with aspergillosis or positive rheumatoid factor. The study concludes that the LFA is a useful tool for detecting cryptococcal antigenemia in severely immunocompromised AIDS patients due to its high NPV, specificity, and PPV.

Cryptococcosis at the university hospital of Marseille: A case series

Cryptococcosis is a fungal infection burdened by a high case-fatality rate in immunocompromised patients. Once limited to human immunodeficiency virus (HIV)-infected patients, the epidemiology of cryptococcosis has evolved in recent years and new risk factors have emerged. It is therefore essential to identify these risk factors in order to improve prevention and therapeutic efficacy. We conducted a retrospective observational study including all cases of cryptococcosis between January 2016 and December 2022, diagnosed at the University Hospital of Marseille. During the study period 15 cases of cryptococcosis were diagnosed. Six patients were HIV-infected. Nine patients had one or more comorbidities including liver cirrhosis, type 2 diabetes mellitus, primary immunodeficiency disorder, chronic lymphocytic leukemia and solid organ transplantation. Ten patients had central nervous system cryptococcosis, four had pulmonary cryptococcosis and one patient had extra-pulmonary disseminated cryptococcosis. Of the three patients with liver cirrhosis, two patients died with a post-mortem diagnosis. Our data suggest that emerging risk factors are probably underestimated by clinicians. It emphasizes the need for cryptococcal antigenemia as part of syndromic investigation of any unexplained fever or neurological symptoms in an at-risk patient. Early diagnosis and treatment are essential for patient's survival.

Baseline C-reactive Protein as a Risk Factor for Cryptococcal Meningitis and Death in HIV-associated Cryptococcal Antigenemia With CrAg Titer as an Effect Modifier.

Persons with HIV and cryptococcal antigenemia are at high risk of progression to cryptococcal meningitis or death. Baseline cryptococcal antigen (CrAg) plasma titer ≥1:160 is a known risk factor for poor outcomes, but other risk factors are unknown. In HIV-associated cryptococcal meningitis, baseline serum C-reactive protein (CRP) concentrations are positively associated with increased mortality. We hypothesized that CRP might also be associated with meningitis or death in persons with cryptococcal antigenemia. We measured plasma CrAg titers and CRP concentrations on cryopreserved serum from prospectively enrolled persons with HIV and cryptococcal antigenemia. Using time-to-event analyses, we compared 24-week meningitis-free survival in persons with normal CRP (<8 mg/L) and elevated CRP (≥8 mg/L). Logistic regression was used to assess how CRP concentration and CrAg titer might interact as covariates. Of the 94 persons with elevated CRP, 19 (20.2%) developed meningitis or death, whereas of the 88 persons with normal CRP, 8 (9.1%) developed meningitis or death (P = .035). Persons with CrAg titer <1:160 and normal CRP had an ∼5% (3/61) event rate, whereas those with CrAg titer <1:160 but elevated CRP had an ∼20% (12/59) event rate. Importantly, we identified a statistically significant interaction effect between CrAg titer and CRP groups, in which elevated CRP increased risk in the low CrAg titer group (odds ratio, 1.54; 95% confidence interval, 1.16-2.04), but this effect was not present in high CrAg titer group (odds ratio, 0.78; 95% confidence interval, .53-1.15). Our findings demonstrate that CrAg titer may modify the direction of effect of CRP with meningitis-free survival; future studies should account for this interaction.

Correction: High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique

Correction: High burden of cryptococcal antigenemia and meningitis among patients presenting at an emergency department in Maputo, Mozambique

Frequency of cryptococcal antigenemia in hiv treatment naïve patients with CD4 count below 200/ml

Background: Cryptococcosis is a dangerous opportunistic fungal infection that poses a significant threat to individuals with advanced HIV/AIDS and compromised cellular immunity. The objective was to determine the frequency of asymptomatic cryptococcal antigenemia in treatment naïve HIV patients. Material and Methods: This cross-sectional study was conducted at The Indus Hospital and Health Network, Karachi from July to December 2022. We included all consecutive HIV patients of age &gt; 18 years, either gender, who were treatment naïve, with CD4 counts ≤200/μL, and did not have any symptoms of cryptococcal infection. Cryptococcal antigen (CrAg) was tested in blood based on the Direct Agglutination test. Results: A total of 100 HIV patients were enrolled. The mean age was 35.12 ± 10.93 years. The majority (78%) of the subjects were males, and 2/3rd were sexually active; exposure to birds was identified in 31% of patients. Most of the patients enrolled belonged to WHO HIV stage 1 (61%), followed by stage 4 (30%). The median CD4 count was 103.5 (IQR: 56.5 – 126.5) /μL. 48 patients had CD4 count between 101 to 200/μL, while 51 patients had CD4 count ≤100/μL. Only 2 patients were found to have CrAg positive making an overall prevalence of 2%. Both patients had a CD4 count ≤ 100/μL (n = 2/51, 3.9%). 30% of patients had other opportunistic co-infections (n = 30). Conclusion: The prevalence of asymptomatic cryptococcosis in the treatment naïve HIV is low in the Pakistani population. A routine CrAg screening can be individualized and avoided in selected patients with CD4 count &gt;100/μL in a resource-limited country like Pakistan. Keywords: AIDS, HIV stages, Asymptomatic, Opportunistic infection.

Mucormycosis Associated with Global Coronavirus Disease-19 Pandemic: A Study of Fungal Profile from a Tertiary Health-care Center

Background and Aim: In this era of the coronavirus disease (COVID) pandemic, new health issues appear quickly and cause an outbreak in India. Here, we focus on invasive fungal infections (IFA), namely mucormycosis, aspergillosis, and candidiasis. Hence, in this article, we focus on conventional techniques for early diagnosis of fungus to help clinicians start empirical treatment for the patient and take necessary steps thereby. Materials and Methods: This observational study was conducted for 1 month, from May 2021 to June 2021, on 200 patients admitted to our mucormycosis ward. Samples were first examined microscopically using potassium hydroxide (KOH) wet mounts followed by culture on sabouraud dextrose agar and the gross appearance of the growth was observed. Further identification of species was achieved through the use of lactophenol cotton blue mounts and slide culture technique. Results: Out of 200 patients, 65.5% were male and 34.5% female. We divided these patients into three age groups, i.e., 20–30 years (15%), 40–60 years (54%), and 60–80 years (31%). Seventy-four percent of patients presented with a history of diabetes mellitus, 50% had a history of steroids taken in their past, and 48% had a history of oxygen therapy taken at the time of COVID-19 positivity (52%) samples positive for mucormycosis. Forty-one percent were KOH-positive for Mucorales and 35.5% were culture positive. The most commonly isolated fungus was Rhizopus, followed by Mucor, Lichthemia, Aspergillus spp., and Candida spp. Conclusion: To improve test sensitivity and enable early diagnosis, other serum biomarkers such as galactomannan, beta-D-glucan, cryptococcal antigenemia, and blood quantitative polymerase chain reaction for Aspergillus or Mucorales should be implemented.

Using laboratory data to assess the impact of coronavirus (COVID-19) on reflex cryptococcal antigenaemia (CrAg) testing in South Africa.

Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in Wuhan, China. Due to the rapid spread globally, it was declared a pandemic in March 2020. Social distancing and lockdown measures were introduced to limit transmission. These strategies could potentially impact the diagnosis and treatment of patients with advanced HIV who are susceptible to secondary infections like cryptococcal disease. In South Africa, reflexed cryptococcal antigenaemia (CrAg) testing and pre-emptive antifungal treatment are recommended preceding antiretroviral therapy initiation for patients with a CD4<100 cells/μl. This study aimed to assess the impact of COVID-19 on CrAg testing in South Africa. Specimen-level data was extracted for individuals ≥15 years from the National Health Laboratory Services repository for calendar years 2018 to 2021. Test volumes and CrAg positivity were assessed at national and provincial levels, by age category and gender. The percentage change in annual and monthly CrAg test volumes for 2020 and 2021 (during lockdown levels) are compared to data reported for 2018. The monthly median CD4 and the percentage of samples with a count <25, 25-50, 51-75 and >75-<100 cells/μl were assessed. Specimen data of 11 944 929 CD4 results included 1 306 456 CrAg tests. Annual CD4 and CrAg test volumes declined by 22.4% and 27.8% for 2020 and 2021 respectively (relative to 2018). There were 23 670 CrAg positive outcomes in 2018 compared to 21 399 (-9.6%) and 17 847 (-24.6%) in 2020 and 2021 respectively. A monthly test volume reduction of up to 36.6%, 35.5%, 36.1% and 13.3% was reported for infection waves one to four. CrAg detection increased from 6.3% in 2018 to 7.5% in 2020. More testing was offered to males (>56%) with a higher detection rate of 8.1% in 2020. Between 81.0% and 81.8% of testing was for patients aged 20 to 49 years. The monthly percentage of specimens <25 cells/μl ranged from 30.2% (June 2019) to 35.3% (August 2020). Overall, the monthly median CD4 ranged from 39 (IQR: 15-70)(August 2020) to 45 (IQR: 19-72)(March 2019) cells/μl. In 2020, the provincial percentage change in CrAg test volumes ranged from 2.9% to -33.7%. Our findings confirmed the impact of lockdown measures on both the absolute number of CrAg tests performed and detection (increase in 2020). A smaller impact on the median CD4 was noted. The long-term impact on patient management in immune- compromised individuals needs further investigation.

High prevalence of central nervous system cryptococcosis using a fingerprick whole-blood lateral flow assay in individuals with neurological symptoms and advanced HIV disease in a Brazilian emergency department.

Timely diagnosis is key in managing central nervous system (CNS) cryptococcosis in people living with HIV/AIDS (PLWHA). There are few data on implementing fingerprick whole-blood cryptococcal antigen (CrAg) lateral flow assay (LFA) as the first test for diagnosing CNS cryptococcosis. We evaluated the prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood in a referral emergency department (ED) in São Paulo, Brazil. This was a prospective cohort study of consecutive adult PLWHA with advanced HIV disease and neurological symptoms. Fingerprick whole-blood CrAg LFA was performed at bedside. Seventy-four individuals were enrolled (median age=40 years; males=62%). Prevalence of CNS cryptococcosis was 17.6% (13/74); 95% confidence interval (CI), 9.4-30.0%, and prevalence of positive fingerprick whole-blood CrAg LFA was 25.7% (19/74); 95% CI, 15.5-40.1%. Among the six (8.1%) patients with positive fingerprick whole-blood CrAg LFA and negative CSF CrAg LFA, four (5.4%) had isolated asymptomatic cryptococcal antigenemia, one (1.3%) had symptomatic cryptococcal antigenemia, and one (1.3%) had cryptococcemia. Prevalence of CNS cryptococcosis and cryptococcal antigenemia using fingerprick whole-blood CrAg LFA was high. Point-of-care testing was important for diagnosing CNS cryptococcosis in an ED from a middle-income country.

Cryptococcal antigenemia in a Nigerian child with advanced HIV disease: a case report

Cryptococcal infection in Nigeria’s advanced HIV disease (AHD) population is not uncommon but is sparsely reported in children. The dearth of data on cryptococcal disease in our paediatric population suggests it is an uncommon clinical entity and may cause delayed diagnosis and preventable deaths. It is pertinent that cognizance be done of this clinical entity in our paediatric population. We report a 16-month-old HIV-positive child with complaints of weight loss of 3 months, cough of 1 month, fever, passage of watery stool, fast and difficulty in breathing for 1 week. She was initially managed as a case of paediatric AIDS with septicaemia and was receiving ceftriaxone and cotrimoxazole. The diagnosis was subsequently reviewed to paediatric AIDS with cryptococcal disease as the cryptococcal antigen screening test was positive and oral fluconazole commenced. However, the patient deteriorated and eventually died. This case report suggests a significant knowledge gap in the occurrence of cryptococcosis in our paediatric population and as a matter of urgency the need to conduct studies targeted at ascertaining the burden of cryptococcosis in children living with AHD in Nigeria.

Implementation of point-of-care testing and prevalence of cryptococcal antigenaemia among patients with advanced HIV disease in Mumbai, India

ObjectivesTo describe the implementation of screening for cryptococcal antigenaemia by point-of-care (POC) serum cryptococcal antigen (CrAg) lateral flow assay, measure the prevalence and factors associated with serum cryptococcal antigenaemia in...

Cryptococcosis in non-HIV/non-transplant hematological patients: A 12-year retrospective clinical analysis in a Peruvian referral cancer center.

e19536 Background: Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in non-HIV/non-transplant oncohematological patients. Methods: We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2018. We exclude HIV and transplant recipients patients. Results: During the 12-year study period, among 14908 individuals with hematological malignancies (HM), a total of 21 cases of cryptococcosis were identified, representing an incidence rate of 1.41 per 1000 HM diagnosed in our center. Non-Hodgkin lymphoma (NHL) (47.6%), acute leukemias (23.8%), multiple myeloma (19.1%), and Hodgkin lymphoma (9.5%). Three cases of adult T-cell leukemia/lymphoma were identified. The sub-group analysis showed that NHL (7.35 per 1000 NHL) and Multiple myeloma (4.59 per 1000 MM) had the highest incidence rates. Regarding the clinical presentation, the time between the diagnosis of cryptococcosis and HM was 42 (18–161) days. Cryptococcal fungemia and antigenemia was the most frequent diagnosis (85.7%), followed by pulmonary (52.4%) and central nervous system (38.1%) involvement. At the time of the diagnosis of cryptococcosis, 61.5% were receiving chemotherapy, 53.9% were in the induction phase, and 7.7% were on maintenance therapy. The use of immunosuppressants and chemotherapy within a month of the diagnosis of cryptococcosis was the most common risk factor (90.5%). Regarding the subanalysis performed between the different types of malignancies (NHL versus other HM), age at admission (p = 0.02), site of cryptococcosis presentation (p = 0.01), and lymphocyte count at admission (p = 0.01) were statistically different between these groups. In the NHL subgroup, there was less involvement of the lungs and higher fungemia (p = 0.01). The overall survival (OS) of our cohort at 15 and 120 days was 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other HM was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions: Our cohort characterized the distinct clinical presentation, risk factors, and outcomes of cryptococcal infection in hematologic malignancies subgroups. NHL was the HM with the worst prognosis and the highest incidence rate. [Table: see text]

Six months survival and risk factors for attrition for patients detected with cryptococcal antigenemia through screening in Malawi.

A cohort of adult Malawian people living with HIV (PLHIV) testing positive for cryptococcal antigenemia was observed and followed to determine the outcomes and risk factors for attrition. Eligible PLHIV were enrolled at 5 health facilities in Malawi, representing different levels of health care. ART naïve patients, ART defaulters returning to care, and patients with suspected or confirmed ART treatment failure with CD4 <200 cells/μL or clinical stage 3 or 4 were enrolled and received CrAg tests on whole blood specimens from August 2018 to August 2019. Hospitalized PLHIV were enrolled and tested for CrAg from January 2019 to August 2019, regardless of CD4 or clinical stage. Patients with cryptococcal antigenemia were managed per Malawian clinical guidelines and were followed up for six months. Survival and risk factors for attrition at six months were assessed. A total of 2146 patients were screened and 112 (5.2%) had cryptococcal antigenemia. Prevalence ranged from 3.8% (Mzuzu Central Hospital) to 25.8% (Jenda Rural Hospital). Of the 112 patients with antigenemia, 33 (29.5%) were diagnosed with concurrent CM at the time of enrollment. Six-month crude survival of all patients with antigenemia (regardless of CM status) ranged from 52.3% (assuming lost-to-follow-up (LTFU) patients died) to 64.9% (if LTFU survived). Patients who were diagnosed with concurrent CM by CSF test had poor survival (27.3-39.4%). Patients with antigenemia who were not diagnosed with concurrent CM had 71.4% (if LTFU died)- 89.8% (if LTFU survived) survival at six months. In adjusted analyses, patients with cryptococcal antigenemia detected after admission to inpatient care (aHR: 2.56, 1.07-6.15) and patients with concurrent CM at the time of positive antigenemia result (aHR: 2.48, 1.04-5.92) had significantly higher hazard of attrition at six months. Overall, our findings indicate a need for routine access to CrAg screening and pre-emptive fluconazole treatment as a way to detect cryptococcal antigenemia and prevent CM in outpatient and inpatient settings. Rapid access to diagnosis and treatment for cryptococcal meningitis (CM) with gold-standard antifungals is needed to improve survival of patients with advanced HIV in Malawi.

The incidence of histoplasmosis and cryptococcal antigenemia among patients attending a large HIV clinic in Trinidad

Our aim was to determine the incidence disseminated histoplasmosis and cryptococcal antigenemia among 280 patients with a CD4<350 cells/mm3 attending a large HIV clinic in Trinidad over the period November 2021-June 2022. Sera were screened for cryptococcal antigen (CrAg) using the Immy CrAg Immunoassay (EIA) and the Immy CrAg lateral flow assay (LFA). Urine was screened for Histoplasma antigen using the Immy EIA and the Optimum Imaging Diagnostics (OIDx) LFA. For the purposes of analysis, it was assumed, that all patients with positive urine Histoplasma antigen tests by both EIA and LFA and those with a single positive urine Histoplasma antigen test and clinical features of disseminated histoplasmosis were true positives. The incidence of probable disseminated histoplasmosis and cryptococcal antigenemia were 6.4% (18/280) and 2.5% (7/280) respectively. The sensitivity and specificity of the Immy Histoplasma EIA were 100% (95% CI, 81.5%-100%) and 98.5% (95% CI, 96.1% - 99.6%) respectively as compared to the OIDx Histoplasma LFA of 88.9% (95% CI, 65.3% - 98.6%) and 93.9% (95% CI, 90.3% - 96.5%) respectively, with substantial agreement between the 2 test kits (Kappa value = 0.763; 95% CI 0.685, 0.841). Testing for disseminated histoplasmosis in HIV patients is important in endemic areas.

Cryptococcal antigenaemia amongst HIV infected children in Owerri, South East Nigeria

Objective: Cryptococcosis is an opportunistic infection caused by Cryptococcus and can result in cryptococcal meningitis, which is an AIDS-defining condition associated with high morbidity and mortality. Although a high prevalence of Cryptococcal antigenemia (CrAg) preceding cryptococcal disease has been reported in HIV-infected Nigerian adults, it is more common in patients with low CD4, stage 3 or 4 HIV. However, there is only one study on Cryptococcal antigenemia in HIV-infected Nigerian children. Therefore, this study aimed to determine the burden of cryptococcosis in HIV-infected children. Material and Methods: This study was a hospital-based cross-sectional study conducted between October 2018 and January 2019 at the Pediatric Infectious Disease Clinic of the Federal Medical Centre, Owerri. The study population consisted of HIV-infected children (aged 2-16 years) attending the clinic. The subjects were recruited consecutively and underwent a thorough physical examination and anthropometric measurements before a single blood sample was taken. Cryptococcal antigen was assayed using the Lateral Flow Assay method, and CD4+ counts were assayed using cyflow. Results: A total of 100 children were involved in the study, of which 51 (51%) were female and 49 (49%) were male (M:F, 1:1). The average age of the participants was 9.73 ± 3.12 years. Among the 100 children tested, there was no cryptococcal antigenemia (0%). Statistical analysis was limited to simple description. Conclusion: Cryptococcosis is not a common opportunistic infection among HIV-infected children attending the Pediatric Infectious Disease Clinic in Federal Medical Centre Owerri. Therefore, it may not be considered as a differential diagnosis for HIV-positive children with meningoencephalitis.

Hyponatremia as a Predictor of Cryptococcal Meningitis and Death Among Asymptomatic Persons With HIV and Cryptococcal Antigenemia.

Among persons with human immunodeficiency virus-associated cryptococcal meningitis serum hyponatremia is a risk factor for mortality; however, the role of hyponatremia in persons with asymptomatic cryptococcal antigenemia is unknown. We found that serum hyponatremia ≤130 mmol/L is an independent risk factor for progression to meningitis and death in asymptomatic persons with cryptococcal antigenemia.

A multicenter survey of asymptomatic cryptococcal antigenemia among patients with advanced HIV disease in Nigeria.

As of 2018, cryptococcal antigen (CrAg) screening in patients with advanced human immunodeficiency virus (HIV) disease (AHD) was not routinely implemented in Nigeria despite being recommended in the national HIV treatment guidelines. Our aim was to determine the prevalence and risk factors for asymptomatic cryptococcal antigenemia in adult people living with HIV (PLHIV) in Nigeria to advocate for the implementation of routine CrAg screening. A descriptive cross-sectional study and CrAg screening of consecutive adult PLHIV with CD4 counts ≤200 cells/μL was conducted from April 2018 to April 2019 at HIV clinics in eleven tertiary hospitals spread across Nigeria's six geopolitical regions. Prevalence of asymptomatic cryptococcal antigenemia was estimated by facility and geopolitical zone. Logistic regression was conducted to identify risk factors for cryptococcal antigenemia. In total, 1,114 patients with AHD were screened. The overall prevalence of asymptomatic cryptococcal antigenemia was 3.9% with wide variation across facilities (range: 0/75 [0%]- 15/122 [12.3%]) and geopolitical zones (range: 0/75 [0%]-19/279 [6.8%]). Prevalence of antigenemia was highest in the South-West (19/279 [6.8%]) and lowest in the North-East (0/75 [0%]). Prevalence was 5.2% (26/512) and 3.2% (18/561) in patients with CD4<100 and CD4 of 101-200, respectively. Of all patients with antigenemia, 50% were on antiretroviral therapy (ART) at the time of having a positive CrAg test. In adjusted analysis, cryptococcal antigenemia was significantly less in patients on ART and patients who had completed any formal education. The survey showed a high overall burden of cryptococcal antigenemia in Nigeria, with variable prevalence across geopolitical regions. We provided valuable evidence for implementing routine CrAg screening of AHD patients in Nigeria which has commenced in selected centres.

Prevalence and Associated Factors of Cryptococcal Antigenemia in HIV-Infected Patients with CD4 < 200 Cells/µL in São Paulo, Brazil: A Bayesian Analysis

Cryptococcosis is a severe life-threatening disease and a major cause of mortality in people with advanced AIDS and CD4 ≤ 100 cells/µL. Considering the knowledge gap regarding the benefits of routine application of antigenemia tests in HIV-infected patients with 100−200 CD4 cells/µL for the prevention of cryptococcal meningitis (CM), we aimed to evaluate the prevalence of positive antigenemia through lateral flow assay (LFA) and associated factors in HIV-infected patients with CD4 < 200 cells/µL. Our findings of 3.49% of positive LFA (LFA+) patients with CD4 < 100 cells/µL and 2.24% with CD4 between 100−200 cells/µL have been included in a Bayesian analysis with 12 other studies containing similar samples worldwide. This analysis showed a proportion of 3.6% LFA+ patients (95% credible interval-Ci [2.5−5.7%]) with CD4 < 100 cells/µL and 1.1% (95%Ci [0.5−4.3%]) with CD4 between 100−200 cells/µL, without statistical difference between these groups. The difference between mortality rates in LFA+ and negative LFA groups was e = 0.05013. Cryptococcoma and CM were observed in the LFA+ group with 100−200 and <100 CD4 cells/µL, respectively. Considering the benefits of antifungal therapy for LFA+ patients, our data reinforced the recommendation to apply LFA as a routine test in patients with 100−200 CD4 cells/µL aiming to expand cost-effectiveness studies in this group.