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Background Cryptococcal meningitis is a common cause of AIDS-related mortality. Although symptom recurrence after initial treatment is common, the etiology is often difficult to decipher. We sought to summarize characteristics, etiologies, and outcomes among persons with second-episode symptomatic recurrence. Methods We prospectively enrolled Ugandans with cryptococcal meningitis and obtained patient characteristics, antiretroviral therapy (ART) and cryptococcosis histories, clinical outcomes, and cerebrospinal fluid (CSF) analysis results. We independently adjudicated cases of second-episode meningitis to categorize patients as (1) microbiological relapse, (2) paradoxical immune reconstitution inflammatory syndrome (IRIS), (3) persistent elevated intracranial pressure (ICP) only, or (4) persistent symptoms only, along with controls of primary cryptococcal meningitis. We compared groups with chi-square or Kruskal-Wallis tests as appropriate. Results 724 participants were included (n = 607 primary episode, 81 relapse, 28 paradoxical IRIS, 2 persistently elevated ICP, 6 persistent symptoms). Participants with culture-positive relapse had lower CD4 (25 cells/μL; IQR: 9–76) and lower CSF white blood cell (WBC; 4 cells/μL; IQR: 4–85) counts than paradoxical IRIS (CD4: 78 cells/μL; IQR: 47–142; WBC: 45 cells/μL; IQR: 8–128). Among those with CSF WBC <5 cells/μL, 86% (43/50) had relapse. Among those with CD4 counts <50 cells/μL, 91% (39/43) had relapse. Eighteen-week mortality (from current symptom onset) was 47% among first episodes of cryptococcal meningitis, 31% in culture-positive relapses, and 14% in paradoxical IRIS. Conclusions Poor immune reconstitution was noted more often in relapse than IRIS as evidenced by lower CSF WBC and blood CD4 counts. These easily obtained laboratory values should prompt initiation of antifungal treatment while awaiting culture results. Clinical Trials Registration NCT01802385. [ABSTRACT FROM AUTHOR]

The article discusses the World Health Organization guidelines for recommending cryptococcal antigen (CrAg) screening in blood for human immunodeficiency virus (HIV)-infected persons, who do not receive effective antiretroviral therapy. It mention the asymptomatic CrAg-positive patients being enrolled in the ORCAS study during fluconazole therapy.

Background: HIV-infected persons with detectable cryptococcal antigen (CrAg) in blood have increased morbidity and mortality compared with HIV-infected persons who are CrAg-negative. This study examined neurocognitive function among persons with asymptomatic cryptococcal antigenemia.Methods: Participants from three prospective HIV cohorts underwent neurocognitive testing at the time of antiretroviral therapy (ART) initiation. Cohorts included persons with cryptococcal meningitis (N = 90), asymptomatic CrAg + (N = 87), and HIV-infected persons without central nervous system infection (N = 125). Z-scores for each neurocognitive test were calculated relative to an HIV-negative Ugandan population with a composite quantitative neurocognitive performance Z-score (QNPZ-8) created from eight tested domains. Neurocognitive function was measured pre-ART for all three cohorts and additionally after 4 weeks of ART (and 6 weeks of pre-emptive fluconazole) treatment among asymptomatic CrAg + participants.Results: Cryptococcal meningitis and asymptomatic CrAg + participants had lower median CD4 counts (17 and 26 cells/μL, respectively) than the HIV-infected control cohort (233 cells/μL) as well as lower Karnofsky performance status (60 and 70 vs. 90, respectively). The composite QNPZ-8 for asymptomatic CrAg + (-1.80 Z-score) fell between the cryptococcal meningitis cohort (-2.22 Z-score, P = 0.02) and HIV-infected controls (-1.36, P = 0.003). After four weeks of ART and six weeks of fluconazole, the asymptomatic CrAg + cohort neurocognitive performance improved (-1.0 Z-score, P < 0.001).Conclusion: Significant deficits in neurocognitive function were identified in asymptomatic CrAg + persons with advanced HIV/AIDS even without signs or sequelae of meningitis. Neurocognitive function in this group improves over time after initiation of pre-emptive fluconazole treatment and ART, but short term adherence support may be necessary. [ABSTRACT FROM AUTHOR]

Most studies evaluating epidemiologic relationships between helminths and HIV have been conducted in the pre-ART era, and evidence of the impact of helminth infections on HIV disease progression remains conflicting. Less is known about helminth infection and clinical outcomes in HIV-infected adults receiving antiretroviral therapy (ART). We sampled HIV-infected adults for eight gastrointestinal parasites and correlated parasitic infection with demographic predictors, and clinical and immunologic outcomes. Contrasting with previous studies, we measured parasitic infection with a quantitative, highly sensitive and specific polymerase chain reaction (PCR) method. This cohort study enrolled HIV-infected Ugandans from August-September 2013 in Mbale, Uganda and collected stool and blood samples at enrollment. Real-time PCR quantified stool: Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica, and Giardia intestinalis infection. Generalized linear models assessed relationships between parasitic infection and clinical or demographic data. 35% of participants (71/202) tested positive for ≥1 helminth, mainly N. americanus (55/199, 28%), and 4.5% (9/202) were infected with ≥2 stool parasites. Participants with hookworm infection had lower average CD4+ cell counts (-94 cells/mcL, 95%CI: -141, -48 cells/mcL; p<0.001) after adjustment for sex, CD4+ nadir at clinic entry, and time on ART. The high prevalence of parasitic infection and correlation with decreased CD4+ concentrations highlight the need to re-examine the effects of invasive helminth co-infection in rural, HIV-infected populations in the era of widely available ART. Elucidating the relationship between hookworm infection and immune recovery could provide opportunities for health optimization, e.g. integrated deworming, in these vulnerable populations. [ABSTRACT FROM AUTHOR]

The effect of tenofovir and amphotericin coadministration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4 weeks after diagnosis in Ugandans undergoing cryptococcal meningitis therapy and classified as not receiving antiretroviral therapy (ART), receiving nontenofovir ART or receiving tenofovir-based ART. Longitudinal creatinine changes and grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks after diagnosis, creatinine was 0.25 mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin coadministration did not increase the risk of kidney dysfunction. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The Oncotype DX Genomic Prostate Score (ODX‐GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX‐GPS uptake.Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3 + 3 or 3 + 4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX‐GPS data. Census‐tract level neighborhood socioeconomic status (nSES) quintiles were constructed using a composite socioeconomic score. Multivariable logistic regression was used to estimate the associations of ODX‐GPS uptake with age at diagnosis, race and ethnicity, nSES, geographic region, insurance type, and marital status, accounting for National Comprehensive Cancer Network risk group, year of diagnosis, and clustering by census tract.Among 111,434 eligible men, 5.5% had ODX‐GPS test uptake. Of these, 78.3% were non‐Hispanic White, 9.6% were Black, 6.7% were Hispanic, and 3.6% were Asian American. Black men had the lowest odds of ODX‐GPS uptake (odds ratio, 0.70; 95% confidence interval [CI], 0.63–0.76). Those in the highest versus lowest quintile of nSES were 1.64 times more likely (95% CI, 1.38–2.94) to have ODX‐GPS uptake. The odds of ODX‐GPS uptake were statistically significantly higher among men residing in the Northeast, West, and Midwest compared to the South.Disparities in ODX‐GPS uptake by race, ethnicity, nSES, and geographical region were identified. Concerted efforts should be made to ensure that this clinical test is equitably available. [ABSTRACT FROM AUTHOR]

Background: Precision medicine has become a mainstay of cancer care in recent years. The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program has been an authoritative source of cancer statistics and data since 1973. However, tumor genomic information has not been adequately captured in the cancer surveillance data, which impedes population-based research on molecular subtypes. To address this, the SEER Program has developed and implemented a centralized process to link SEER registries' tumor cases with genomic test results that are provided by molecular laboratories to the registries., Methods: Data linkages were carried out following operating procedures for centralized linkages established by the SEER Program. The linkages used Match*Pro, a probabilistic linkage software, and were facilitated by the registries' trusted third party (an honest broker). The SEER registries provide to NCI limited datasets that undergo preliminary evaluation prior to their release to the research community., Results: Recently conducted genomic linkages included OncotypeDX Breast Recurrence Score, OncotypeDX Breast Ductal Carcinoma in Situ, OncotypeDX Genomic Prostate Score, Decipher Prostate Genomic Classifier, DecisionDX Uveal Melanoma, DecisionDX Preferentially Expressed Antigen in Melanoma, DecisionDX Melanoma, and germline tests results in Georgia and California SEER registries., Conclusions: The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI's SEER Program enables scientists to investigate numerous research inquiries., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Immunosuppressed individuals have elevated risk of virus-related cancers. Identifying cancers with elevated risk in people with HIV (PWH) and solid organ transplant recipients (SOTRs), two immunosuppressed populations, may help identify novel etiologic relationships with infectious agents., Methods: We utilized two linkages of population-based cancer registries with HIV and transplant registries in the United States. Cancer entities were systematically classified based on site and histology codes. Standardized incidence ratios (SIRs) were used to compare risk in PWH and SOTRs with the general population. For selected cancer entities, incidence rate ratios (IRRs) were calculated for indicators of immunosuppression within each population., Findings: We identified 38,047 cancer cases in SOTRs and 53,592 in PWH, yielding overall SIRs of 1.66 (95%CI = 1.65-1.68) and 1.49 (95%CI = 1.47-1.50), respectively. Forty-three cancer entities met selection criteria, including conjunctival squamous cell carcinoma (SCC) (PWH SIR = 7.1, 95%CI = 5.5-9.2; SOTRs SIR = 9.4; 95%CI = 6.8-12.6). Sebaceous adenocarcinoma was elevated in SOTRs (SIR = 16.2; 95%CI = 14.0-18.6) and, among SOTRs, associated with greater risk in lung/heart transplant recipients compared to recipients of other organs (IRR = 2.3; 95%CI = 1.7-3.2). Salivary gland tumors, malignant fibrous histiocytoma (MFH), and intrahepatic cholangiocarcinoma showed elevated risk in SOTRs (SIR = 3.9; SIR = 4.7; and SIR = 3.2, respectively) but not in PWH. However, risks for these cancers were elevated following an AIDS diagnosis among PWH (IRR = 2.4; IRR = 4.3; and IRR = 2.0, respectively)., Interpretation: Elevated SIRs among SOTRs and PWH, and associations with immunosuppression within these populations, suggest novel infectious causes for several cancers including conjunctival SCC, sebaceous adenocarcinoma, salivary gland tumors, MFH, and intrahepatic cholangiocarcinoma., (Published by Oxford University Press 2024.)

Background: Disparities in cancer burden and outcomes according to socioeconomic characteristics have been extensively characterized for US populations. The cancer experience of refugees, who may share characteristics of other socioeconomically disadvantaged populations and also experience distinct barriers to care, has not been described previously. We conducted a proof-of-concept study evaluating our ability to characterize cancer incidence in refugees resettled to Idaho via a novel linkage of cancer data and administrative data characterizing refugee arrivals to Idaho., Methods: In July 2021, the Cancer Data Registry of Idaho probabilistically linked cancer surveillance data and refugee arrival data (2008- 2019 diagnosis and arrival years) collected through the Centers for Disease Control and Prevention's Electronic Disease Notification (EDN) System. We used SEER*Stat to calculate standardized incidence ratios (SIR) for malignant tumors and benign/borderline malignant brain and other nervous system (ONS) tumors using Idaho-specific and Surveillance, Epidemiology, and End Results (SEER) Program referent incidence rates., Results: 60 malignant and 7 benign brain and ONS tumors were diagnosed among 9,499 refugees resettled to Idaho. Refugees had fewer than expected malignant tumors overall (57 observed vs 96.0 expected; SIR, 0.60; 95% CI, 0.45-0.77). An excess of tumors of the esophagus were diagnosed among Southeast Asian refugees (4 observed vs 0.64 expected; SIR, 6.3; 95% CI, 1.7-16.0). We also used EDN data to update country of birth for linked persons., Conclusions: Linking EDN refugee data to cancer surveillance data presented unique challenges. However, we used a novel data source to augment cancer data and characterize incidence in refugees, potentially improving our ability to serve this vulnerable population.

Background: Produce-associated outbreaks of Shiga toxin-producing Escherichia coli (STEC) were first identified in 1991. In April 2018, New Jersey and Pennsylvania officials reported a cluster of STEC O157 infections associated with multiple locations of a restaurant chain. The Centers for Disease Control and Prevention (CDC) queried PulseNet, the national laboratory network for foodborne disease surveillance, for additional cases and began a national investigation., Methods: A case was defined as an infection between 13 March and 22 August 2018 with 1 of the 22 identified outbreak-associated E. coli O157:H7 or E. coli O61 pulsed-field gel electrophoresis pattern combinations, or with a strain STEC O157 that was closely related to the main outbreak strain by whole-genome sequencing. We conducted epidemiologic and traceback investigations to identify illness subclusters and common sources. A US Food and Drug Administration-led environmental assessment, which tested water, soil, manure, compost, and scat samples, was conducted to evaluate potential sources of STEC contamination., Results: We identified 240 case-patients from 37 states; 104 were hospitalized, 28 developed hemolytic uremic syndrome, and 5 died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty subclusters were identified. Product traceback from subcluster restaurants identified numerous romaine lettuce distributors and growers; all lettuce originated from the Yuma growing region. Water samples collected from an irrigation canal in the region yielded the outbreak strain of STEC O157., Conclusions: We report on the largest multistate leafy greens-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination., (Published by Oxford University Press for the Infectious Diseases Society of America 2019.)

Background: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS., Methods: We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps., Results: We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160., Conclusions: We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.

Introduction: Improving HIV outcomes among severely immunocompromised HIV-infected persons who have increased morbidity and mortality remains an important issue in sub-Saharan Africa. We sought to evaluate the impact of targeted clinic-based nurse care on antiretroviral therapy (ART) initiation and retention among severely immunocompromised HIV-infected persons., Methods: The study included ART-naive patients with CD4 counts <100 cells per microliter registered in seven urban clinics in Kampala, Uganda. Data were retrospectively collected on patients enrolled from July to December 2011 (routine care cohort). Between July 2012 and September 2013, 1 additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation, and trace those who were lost to follow-up. We compared time to ART initiation and 6-month retention in care between cohorts and used a generalized linear model to estimate the relative risk of retention., Results: The study included 258 patients in the routine care cohort and 593 in the nurse counselor cohort. The proportion of patients who initiated ART increased from 190 (73.6%) in the routine care cohort to 506 (85.3%) in the nurse counselor cohort (P < 0.001). At 6 months, 62% of the routine care cohort were retained in care versus 76% in the nurse counselor cohort (P = 0.001). A 21% increase in the likelihood of retention in the nurse counselor cohort (relative risk: 1.21, 95% CI: 1.09 to 1.34) compared with the routine care cohort was observed., Conclusions: Implementation of targeted nurse-led care of severely immunocompromised HIV-infected patients in public outpatient health care facilities resulted in decreased time to ART initiation and increased retention.

The effect of tenofovir and amphotericin coadministration on kidney function is poorly characterized. We measured creatinine during induction therapy and at 4 weeks after diagnosis in Ugandans undergoing cryptococcal meningitis therapy and classified as not receiving antiretroviral therapy (ART), receiving nontenofovir ART or receiving tenofovir-based ART. Longitudinal creatinine changes and grade 2-4 creatinine adverse events were evaluated across groups. Creatinine concentrations were similar across ART groups. At 4 weeks after diagnosis, creatinine was 0.25 mg/dL higher than at diagnosis, but similar across groups. Adverse event incidence was also similar across ART groups. Tenofovir and amphotericin coadministration did not increase the risk of kidney dysfunction.