BACKGROUND: Certain workers are at increased risk for acquiring Legionnaires' disease compared with other workers. This study aims to identify occupations at increased risk for acquiring Legionnaires' disease. METHODS: Using data from the US Centers for Disease Control and Prevention's Supplemental Legionnaires' Disease Surveillance System, this study identified Legionnaires' disease confirmed patients ≥16 years of age in 39 states with reported symptom onset during 2014-2016. Age-adjusted and sex-adjusted incidence rate ratios (IRR) stratified by occupation group were calculated by comparing Legionnaires' disease patients in an occupation group (eg, transportation) to those in all other occupation groups (eg, non-transportation). RESULTS: A total of 2553 patients had a known occupation group. The two occupations with the highest burden were transportation (N=287; IRR=2.11) and construction (N=269; IRR=1.82). Truck drivers comprised the majority (69.7%) of the transportation occupation group and construction labourers comprised almost half (49%) of the construction occupation group. The healthcare support occupation had the highest IRR (N=75; IRR=2.16). CONCLUSION: Transportation and construction workers, who are generally not covered by guidance related to building water systems, have increased risk of Legionnaires' disease compared with other workers. One hypothesised risk factor for truck drivers is the use of non-genuine windshield cleaner in their vehicles. A simple intervention is to use genuine windshield cleaner with bactericidal properties (ie, includes isopropanol/methanol) which can reduce the risk of Legionella growth and transmission. To improve surveillance of Legionnaires' disease and identification of similar exposures, the authors encourage the collection of occupation and industry information for all patients with Legionnaires' disease.

BACKGROUND: Net and crude cancer survival statistics can be calculated using cause of death or expected survival from life tables. In some instances, using cause of death information may be advantageous. The Surveillance, Epidemiology, and End Results (SEER) Program cause-specific cause of death variable (North American Association of Central Cancer Registries [NAACCR] item #1914) designates that a patient died of their cancer. We evaluated how miss-ingness in NAACCR item #1914 impacted survival estimates to determine fitness for use in NAACCR Cancer in North America (CiNA) products. METHODS: We used CiNA survival and prevalence data (November 2020 submission) to calculate 60-month cause-specific survival among persons aged 15-99 years at time of diagnosis using NAACCR item #1914. We treated missing/unknown causes of death in 3 ways: excluded from analysis, included as dead from this cancer, or included as censored at time of last follow-up. Autopsy/death-certificate-only cases were excluded from survival analyses. We calculated the proportion of deaths with unknown/missing cause of death by registry and demographic variables. RESULTS: Generally, 60-month cause-specific survival estimates differed by <1% between the 3 approaches when NAACCR item #1914 was missing/unknown for <3% of deaths. When applying a <3% fit-for-use standard to SEER cause-specific cause of death, data from 34 registries were included in cause-specific survival analyses. The proportion of deaths with missing/unknown cause of death varied by primary site, age at diagnosis, race/ethnicity, year of diagnosis, and registry. CONCLUSION: We have identified missingness cut points for NAACCR item #1914, which strike a balance between scientific integrity and registry inclusiveness, to designate data in NAACCR CiNA data products as fit for use in cause-specific survival analyses.

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. 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 March 13 and August 22, 2018 with one 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 sub-clusters and common sources. An FDA-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 five died. Of 179 people who were interviewed, 152 (85%) reported consuming romaine lettuce in the week before illness onset. Twenty sub-clusters were identified. Product traceback from sub-cluster 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. CONCLUSION: We report on the largest multistate leafy green-linked STEC O157 outbreak in several decades. The investigation highlights the complexities associated with investigating outbreaks involving widespread environmental contamination.

INTRODUCTION: Progress in U.S. 5-year survival trends for all cancers combined was assessed using the North American Cancer Survival Index, a sum of age-, sex-, and cancer site-standardized relative survival ratios. METHODS: In January 2019, authors calculated 5-year cancer survival indices and 95% CIs by race and sex for 2005-2011, 2006-2012, 2007-2013, and 2008-2014 diagnosis cohorts with data from 42 cancer registries. RESULTS: Overall 5-year survival increased from 63.5% (95% CI=63.4, 63.5) in 2005-2011 to 64.1% (95% CI=64.1, 64.2) in 2008-2014. Survival increased 0.9 and 0.5 percentage points in female and male patients, respectively; the survival disparity among blacks versus whites decreased by 0.5%. In 2008-2014, the Cancer Survival Index was 7.7% higher for whites (64.6%; 95% CI=64.6, 64.7) than for blacks (56.9%; 95% CI=56.7, 57.1). CONCLUSIONS: Cancer Survival Index survival estimates increased among all race and sex subpopulations during 2005-2014. A substantial but decreasing survival gap persisted between blacks and whites. The Cancer Survival Index can assist decision makers and others in comparing cancer survival among populations and over time and in monitoring progress toward national cancer surveillance objectives.

Current World Health Organization (WHO) guidelines recommend cryptococcal antigen (CrAg) screening in blood among those human immunodeficiency virus (HIV)-infected persons not receiving effective antiretroviral therapy (ART), with CD4 values <100 cells/µL, and to consider testing those not on ART with CD4 values between 100–200 cells/µL [1]. This recommendation is based on prior studies demonstrating that a “screen-and-treat” program identifying CrAg-positive persons and giving preemptive fluconazole therapy, in combination with an ART adherence intervention, prevents invasive cryptococcal disease and death [2].

BACKGROUND: HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and pre-emptive fluconazole therapy, as an adjunct to antiretroviral therapy (ART), on six-month survival among persons with advanced HIV disease. METHODS: We enrolled HIV-infected, ART-naive eligible participants with <100 CD4 cells/microL, in a stepped-wedge, cluster-randomized trial from July 2012 - December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with lab-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg-positive participants received preemptive fluconazole therapy for ten weeks. We assessed six-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps. RESULTS: We included 1,280 observational and 2,108 interventional participants, of whom 9.3% (195/2,108) were CrAg-positive. CD4-, time-, and stepped-wedge-adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (HR = 1.34; 95% CI, 0.86-2.10; P = 0.20), including when the analysis was limited to persons who started ART (HR=1.11; 95% CI, 0.62 - 1.79, P=0.86) However, six-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 six-month mortality than patients with titers <1:160. CONCLUSION: We observed no overall survival benefit of the lab-based reflexive CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis appeared to be effective in patients with CrAg titer <1:160. A more aggressive approach may be required for persons with CrAg titer >/=1:160.This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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/muL, respectively) than the HIV-infected control cohort (233 cells/muL) 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.

OBJECTIVES: Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival. METHODS: We used data from Ugandan and South African trial participants to characterize the variation of haemoglobin concentrations from diagnosis to 12 weeks post-diagnosis. Anaemia severity was classified based on the haemoglobin concentration at cryptococcal meningitis diagnosis, and nadir haemoglobin values during amphotericin induction. Cox proportional hazard models were used to estimate 2- and 10-week mortality risk. We also estimated 10-week mortality risk among participants with nadir haemoglobin < 8.5 g/dL during amphotericin induction and who survived ≥ 2 weeks post-enrolment. RESULTS: The median haemoglobin concentration at meningitis diagnosis was 11.5 g/dL [interquartile range (IQR) 9.7-13 g/dL; n = 311] with a mean decline of 4.2 g/dL [95% confidence interval (CI) -4.6 to -3.8; P < 0.001; n = 148] from diagnosis to nadir value among participants with baseline haemoglobin ≥ 8.5 g/dL. The median haemoglobin concentration was 8.1 g/dL (IQR 6.5-9.5 g/dL) at 2 weeks, increasing to 9.4 g/dL (IQR 8.2-10.9 g/dL) by 4 weeks and continuing to increase to 12 weeks. Among participants with haemoglobin < 8.5 g/dL at diagnosis, mortality risk was elevated at 2 weeks [hazard ratio (HR) 2.7; 95% CI 1.5-4.9; P < 0.01] and 10 weeks (HR 1.8; 95% CI 1.1-2.2; P = 0.03), relative to those with haemoglobin ≥ 8.5 g/dL. New-onset anaemia occurring with amphotericin therapy did not have a statistically significant association with 10-week mortality (HR 2.0; 95% CI 0.5-9.1; P = 0.4). CONCLUSIONS: Amphotericin induced significant haemoglobin declines, which were mostly transient and did not impact 10-week mortality. Individuals with moderate to life-threatening anaemia at baseline had a higher mortality risk at 2 and 10 weeks post-enrolment.

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 ART initiation and retention among severely immunocompromised HIV-infected persons. METHODS: The study included ART-naive patients with CD4<100 cells/microL 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, one additional nurse per clinic was hired (nurse counselor cohort) to identify new patients, expedite ART initiation and trace those loss-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 likelihood of retention in the nurse counselor cohort (relative risk 1.21, 95% CI, 1.09-1.34) compared with the routine care cohort was observed. CONCLUSION: 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.