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On February 27, 2020, the Santa Clara County Public Health Department (SCCPHD) identified its first case of coronavirus disease 2019 (COVID-19) associated with probable community transmission (i.e., infection among persons without a known exposure by travel or close contact with a patient with confirmed COVID-19). At the time the investigation began, testing guidance recommended focusing on persons with clinical findings of lower respiratory illness and travel to an affected area or an epidemiologic link to a laboratory-confirmed COVID-19 case, or on persons hospitalized for severe respiratory disease and no alternative diagnosis (1). To rapidly understand the extent of COVID-19 in the community, SCCPHD, the California Department of Public Health (CDPH), and CDC began sentinel surveillance in Santa Clara County. During March 5-14, 2020, four urgent care centers in Santa Clara County participated as sentinel sites. For this investigation, county residents evaluated for respiratory symptoms (e.g., fever, cough, or shortness of breath) who had no known risk for COVID-19 were identified at participating urgent care centers. A convenience sample of specimens that tested negative for influenza virus was tested for SARS-CoV-2 RNA. Among 226 patients who met the inclusion criteria, 23% had positive test results for influenza. Among patients who had negative test results for influenza, 79 specimens were tested for SARS-CoV-2, and 11% had evidence of infection. This sentinel surveillance system helped confirm community transmission of SARS-CoV-2 in Santa Clara County. As a result of these data and an increasing number of cases with no known source of transmission, the county initiated a series of community mitigation strategies. Detection of community transmission is critical for informing response activities, including testing criteria, quarantine guidance, investigation protocols, and community mitigation measures (2). Sentinel surveillance in outpatient settings and emergency departments, implemented together with hospital-based surveillance, mortality surveillance, and serologic surveys, can provide a robust approach to monitor the epidemiology of COVID-19.

Infection prevention and control (IPC) in health care facilities is essential to protecting patients, visitors, and health care personnel from the spread of infectious diseases, including Ebola virus disease (Ebola). Patients with suspected Ebola are typically referred to specialized Ebola treatment units (ETUs), which have strict isolation and IPC protocols, for testing and treatment (1,2). However, in settings where contact tracing is inadequate, Ebola patients might first seek care at general health care facilities, which often have insufficient IPC capacity (3-6). Before 2014-2016, most Ebola outbreaks occurred in rural or nonurban communities, and the role of health care facilities as amplification points, while recognized, was limited (7,8). In contrast to these earlier outbreaks, the 2014-2016 West Africa Ebola outbreak occurred in densely populated urban areas where access to health care facilities was better, but contact tracing was generally inadequate (8). Patients with unrecognized Ebola who sought care at health care facilities with inadequate IPC initiated multiple chains of transmission, which amplified the epidemic to an extent not seen in previous Ebola outbreaks (3-5,7). Implementation of robust IPC practices in general health care facilities was critical to ending health care-associated transmission (8). In August 2018, when an Ebola outbreak was recognized in the Democratic Republic of the Congo (DRC), neighboring countries began preparing for possible introduction of Ebola, with a focus on IPC. Baseline IPC assessments conducted in frontline health care facilities in high-risk districts in Uganda found IPC gaps in screening, isolation, and notification. Based on findings, additional funds were provided for IPC, a training curriculum was developed, and other corrective actions were taken. Ebola preparedness efforts should include activities to ensure that frontline health care facilities have the IPC capacity to rapidly identify suspected Ebola cases and refer such patients for treatment to protect patients, staff members, and visitors.

Supplemental Digital Content is Available in the Text., 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

Infection control and antimicrobial stewardship programs (ICASPs) are essential to reduce the emergence and spread of antimicrobial resistance. The primary objective of this study was to assess the feasibility of extending a commercial off-the-shelf (COTS) software for ICASPs in low- and middle-income countries (LMICs). This project involved three hospitals in Colombia, including Centro Médico Imbanaco, Clínica San Francisco, and DIME Clínica Neurocardiovascular. A COTS platform (ILÚM Health Solutions(™) Kenilworth, NJ) was extended to function in a range of technology settings, and translatable to almost any language. ICASP features were added, including clinical practice guidelines, hand hygiene (HH) documentation, and isolation precaution (IP) documentation. The platform was delivered as a smartphone mobile application (“app”) for both iOS and Android. The app was successfully implemented at all sites, however, full back-end data integration was not feasible at any site. In contrast to the United States, a suite of surveillance tools and physician-focused decision support without patient data proved to be valuable. Language translation processing occurred quickly and incurred minimal costs. HH and IP compliance tracking were the most used features among ICASP staff; treatment guidelines were most often used by physicians. Use of the app streamlined activities and reduced the time spent on ICASP tasks. Users consistently reported positive impressions including simplicity of design, ease of navigation, and improved efficiency. This ICASP app was feasible in limited-resource settings, highly acceptable to users, and represents an innovative approach to antimicrobial resistance prevention.

Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’

Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%-76%) and a specificity of 99.3% (98%-100%) [IMMY] and a sensitivity of 72.4% (57.3%-87.3%) and a specificity of 91.3% (74%-100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted.

Background: Estimating the burden of intestinal colonization with antibiotic-resistant gram-negative bacteria (AR-GNB) is critical to understanding their global epidemiology and spread. We aimed to determine the prevalence of, and risk factors for, intestinal colonization due to AR-GNB in population-based hospital and community settings in Chile. Methods: Between December 2018 and May 2019, we enrolled randomly selected hospitalized adults in 4 tertiary-care public hospitals (Antofagasta, Santiago, Curico and Puerto Montt), and adults residing in a community-based cohort in the rural town of Molina. Following informed consent, we collected rectal swabs and epidemiological information through a standardized questionnaire. Swabs were plated onto MacConkey agar with 2 µg/mL ciprofloxacin or ceftazidime. All recovered morphotypes were identified, and antibiotic susceptibility testing was performed via disk diffusion. The primary outcome was the prevalence of colonization with fluoroquinolone (FQ)- or third-generation cephalosporin (3GC)–resistant GNB. The secondary outcome was the prevalence of colonization with multidrug-resistant (MDR) GNB, defined as GNB resistant to ≥3 antibiotic classes. Categories were not mutually exclusive. Bivariate and multivariate analyses were performed to describe risk factors for colonization with these categories. Results: In total, 775 hospitalized adults and 357 community participants were enrolled, with a median age of 60 years (IQR, 42–72) and 55 years (IQR, 48–62) years, respectively. Among hospitalized participants, the prevalence of colonization with FQ- or 3GC-resistant GNB was 47% (95% CI, 43%–50%) and 41% (95% CI, 38%–45%), respectively, whereas the prevalence of MDR-GNB colonization was 27% (95% CI, 24%–31%). In the community setting, the prevalence of colonization with either FQ-, 3GC-resistant GNB, or MDR-GNB was 40% (95% CI, 34%–45%), 29% (95% CI, 24%– 34%), and 5% (95% CI, 3%–8%), respectively. Independent risk factors for hospital MDR-GNB colonization included the hospital of admission, unit of hospitalization (intensive care units carried the highest risk), in-hospital antimicrobial exposure, comorbidities (Charlson index), and length of stay. In the community setting, recent antibiotic exposure (Conclusions: A high burden of colonization with AR-GNB was observed in this sample of hospitalized and community-dwelling adults in Chile. The high burden of colonization with GNB resistant to commonly used antibiotics such as FQ and 3GC found in community dwellers, suggests that the community may be a relevant source of antibiotic resistance. Efforts to understand relatedness between resistant strains circulating in the community and the hospital are needed.Funding: NoneDisclosures: None

Background: Since 2015, the CDC has supported the development and implementation of healthcare-associated infection (HAI) surveillance in resource-limited settings through technical support of case definitions and methods that are feasible with existing surveillance capacity and integration with clinical care to maximize sustainability and data use for action. Methods: Surveillance initiatives included facility-level implementation programs in Kenya, Sierra Leone, Thailand, and Georgia; larger national or regional network-level projects in India and Vietnam were also supported. For assessment and planning, surveillance capacities were grouped into 3 domains: staff, informatics, and diagnostic capacities. Based on these capacities, simplified case definitions surveillance methodologies were devised to balance resources and effort with the anticipated value and use of findings. Results: There was broad understanding of the importance of HAI surveillance; however, the required resources and other challenges (eg, training, staffing, quality of available data) were underappreciated. Staff capacities were often influenced by a lack of dedicated surveillance staff and limited experience in systematic data collection and analysis. Informatics capacities were generally limited by the lack of digital data management, nonstandardized clinical data collection and storage, and the inability to assign and maintain unique patient identifiers. We found that capacity for diagnostics, a critical component of traditional HAI surveillance systems, was limited by its availability, frequency of use, and inconsistent rationale in clinical care. We found that successful surveillance strategies were generally simple, matched existing capacities, and targeted specific HAI priorities identified by clinical teams. For example, in Kenya and Sierra Leone, participating facilities established, with minimal external support, simplified SSI surveillance among post–caesarean-delivery patients. These initiatives improved integration of surveillance with clinical care through encouraging participation of the clinical team in surveillance and planning. Furthermore, these models directly linked surveillance activities to improved patient care (eg, combined clinical checklists with surveillance data collection forms). Discussion: In resource-limited settings, the local cost and effort required to establish and sustain the necessary infrastructure for HAI surveillance can be substantial. Establishing actionable and sustainable HAI surveillance can be achieved through simplifying HAI surveillance to match existing capacities and can result in valuable surveillance programs, even in very resource-limited settings.Funding: NoneDisclosures: None

No abstract available.

The 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa underscores the need for health care infection prevention and control (IPC) practices to be implemented properly and consistently to interrupt transmission of pathogens in health care settings to patients and health care workers. Training and assessing IPC practices in general health care facilities not designated as Ebola treatment units or centers became a priority for CDC as the number of Ebola virus transmissions among health care workers in West Africa began to affect the West African health care system and increasingly more persons became infected. CDC and partners developed policies, procedures, and training materials tailored to the affected countries. Safety training courses were also provided to U.S. health care workers intending to work with Ebola patients in West Africa. As the Ebola epidemic continued in West Africa, the possibility that patients with Ebola could be identified and treated in the United States became more realistic. In response, CDC, other federal components (e.g., Office of the Assistant Secretary for Preparedness and Response) and public health partners focused on health care worker training and preparedness for U.S. health care facilities. CDC used the input from these partners to develop guidelines on IPC for hospitalized patients with known or suspected Ebola, which was updated based on feedback from partners who provided care for Ebola patients in the United States. Strengthening and sustaining IPC helps health care systems be better prepared to prevent and respond to current and future infectious disease threats.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html).

Bipolaris mould surgical site infections (SSIs) are exceedingly rare. We describe 21 cases of Bipolaris SSIs in pediatric and adult cardiothoracic surgery patients at ten hospitals in Texas, Arkansas, and Florida during 2008-2013. Median case-patient age was 55 years (range: 3 days-82 years), and 19 (90%) were male. Ten (48%) had coronary artery bypass or valve surgery, and seven (33%) had heart transplantation. Fifteen (71%) had more than one cardiothoracic procedure (median: 3, range: 1-11). Thirteen (62%) case-patients (all 5 pediatric patients, and 8 (50%) of 16 adult patients) had delayed sternal closure (chest closed >1 day [median = 8 days; range: 2-22] following the initial cardiothoracic procedure). Thirteen (62%) had mediastinitis. Median time from initial surgery to positive Bipolaris culture was 20 days (range: 6-497). Sixteen (76%) case-patients died.

Background: A recent study using minimally invasive tissue sampling at Chris Hani Baragwanath Academic Hospital (CHBAH), a public tertiary-care hospital in South Africa, reported that 70% of preterm neonatal deaths were due to healthcare-associated infections (HAIs). Based on these findings, CHBAH in collaboration with the CDC conducted an infection prevention and control (IPC) assessment and identified IPC gaps: limited training and mentorship of staff, medication preparation near the patient zone, and inadequate equipment cleaning and a high infection rates. We implemented a program from February 2019 to February 2020 to address these identified gaps, with the aim of reducing the neonatal sepsis rate. Methods: We focused our interventions on 3 essential activities in the neonatal wards: (1) conducting medication compounding in a safe environment with dedicated trained clinical pharmacy personnel; (2) improving cleaning and reprocessing of medical equipment through use of dedicated ward assistants; and (3) improving infection control–related behavior of frontline healthcare staff through on-site IPC mentorship and training. We captured data on process measures including medication errors and hand hygiene and outcome measures. We also looked at rates of infection, defined as positive cultures from blood and CSF per 1,000 patient days. Results: A NICU satellite pharmacy was established in February 2019 and was managed by a lead pharmacist and pharmacy assistants. Following the intervention, medication errors were reduced from 17% in March to 2% in September; nursing staff previously dedicated to medication preparation were able to spend more time in patient care. Furthermore, 4 full-time ward-assistants were hired in February 2019, and equipment is now cleaned using a standardized protocol in a dedicated cleaning area. A dedicated IPC team was assembled in January 2019 to develop standard operating procedures and conduct frequent trainings with healthcare personnel on IPC practices. Since these trainings were implemented, hand hygiene compliance improved from 25% to 48% over a 4-month period. There has been no significant change in blood/CSF infection rates from before implementation (2018): 17.7 per 1,000 patient days (95% CI, 16.7–18.8) compared to rate of 19.1 per 1,000 patient days (95% CI, 17.7–20.6) after implementation (March–September 2019), with a rate ratio of 1.08 (95% CI, 0.98–1.19). Conclusions: The impact of this program was demonstrated through process improvements and reduction in medication errors. However, to date there has been no change in the overall infection rates, suggesting that additional IPC interventions are needed or that other factors are contributing to the high infection rates.Funding: NoneDisclosures: None

Background: Antimicrobial resistance (AMR) is an increasingly critical global public health challenge. An initial step in prevention is the understanding of resistance patterns with accurate surveillance. To improve accurate surveillance and good clinical care, we developed training materials to improve the appropriate collection of clinical culture samples in Ethiopia. Methods: Specimen-collection training materials were initially developed by a team of infectious diseases physicians, a clinical microbiologist, and a monitoring and evaluation specialist using a training of trainers (ToT) platform. Revisions after each training session were provided by Ethiopian attendees including the addition of regional and culturally relevant material. The training format involved didactic presentations, interactive practice sessions with participants providing feedback and training to each other and the entire group as well as assessments of all training activities. Results: Overall, 4 rounds of training were conducted from August 2017 to September 2019. The first 2 rounds of training were conducted by The Ohio State University (OSU) staff, and Ethiopian trainers conducted the last 2 rounds. Initial training was primarily in lecture format outlining use of microbiology laboratory findings in clinical practice and steps for collecting specimens correctly. Appropriate specimen collection was demonstrated and practiced. Essential feedback from this early audience provided input for the final development of the training manual and visual aids. The ToT for master trainers took place in July 2018 and was conducted by OSU staff. In sessions held in February and August 2019, these master trainers provided training to facility trainers, who provide training to personnel directly responsible for specimen collection. In total, 144 healthcare personnel (including physicians, nurses, and laboratory staff), from 12 representative Ethiopian public and academic hospitals participated in the trainings. Participants were satisfied with the quality of the training (typically ranked >4.5 of 5.0) and strongly agreed that the objectives were clearly defined and that the information was relevant to their work. Posttraining scores increased by 23%. Conclusions: Training materials for clinical specimen collection have been developed for use in low- and middle-resource settings and with initial pilot testing and adoption in Ethiopia. The trainings were well accepted, and Ethiopian personnel were able to successfully lead the trainings and improve their knowledge and skills regarding specimen collection. The materials are being finalized in an online format for easier open access dissemination. Further studies are planned to determine the effectiveness of the trainings in improving the quality of clinical specimen submissions to the microbiology laboratory.Funding: NoneDisclosures: None

Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent one of the most critical emerging antimicrobial-resistance threats globally. Data from low-and middle-income countries (LMICs) are increasingly reported as a part of global efforts to improve surveillance, and they demonstrate a high and increasing burden of CRE. However, containment of CRE using all recommended infection prevention and control (IPC) strategies requires substantial resources, which may be limited in LMICs. We conducted a review of the literature to better understand how approaches to CRE containment in LMICs have varied. Methods: We conducted a literature search using electronic databases (Medline, Embace, Cochrane Library, and Global Health) with no limit to study design or publication year. Search terms consisted of 3 categories: CRE, IPC, and LMIC. Additional publications were also identified from the references of identified articles. Publications were screened for eligibility; non-English articles and studies on other gram-negative organisms were excluded from the analysis. Control measures in included studies were categorized as active surveillance, hand hygiene, contact precautions, isolation, education, environmental control, monitoring and feedback, and other. Results: In total, 2,667 publications were identified using the databases and an additional 24 were manually identified. After deduplicating and screening for eligibility, 27 publications were included in the analysis. Overall, 21 publications (78%) were outbreak reports and 3 (11%) were quasi-experimental studies in settings of high rates of CRE. Also, 23 (85%) described a successful reduction in CRE. Among those 23 publications, 22 publications described adequate descriptions of IPC measures implemented, and the median number of IPC measures was 4.5 (range, 1–8). Environmental control was the most commonly utilized intervention (n = 19, 86%), followed by hand hygiene (n = 14, 64%) and contact precautions (n = 14, 64%). Three publications did not show a reduction in CRE despite the combination of IPC measures (median, 4.5). Overall, 13 publications utilized some method of active surveillance, but complete details on methodology were often lacking. In addition, 4 studies (15%) used only horizontal measures (defined as hand hygiene, environmental control, and/or education) and successfully controlled the CRE outbreaks. Conclusions: Among published reports, successful approaches to CRE control have been reported from LMICs. Use of only horizontal approaches, which are often lower cost and simpler to implement than some vertical strategies, have demonstrated some success; however, additional experience with identifying and implementing cost-effective strategies is needed.Funding: NoneDisclosures: None

Background During the 2014–2016 Ebola epidemic in West Africa, a key epidemiological feature was disease transmission within healthcare facilities, indicating a need for infection prevention and control (IPC) training and support. Methods IPC training was provided to frontline healthcare workers (HCW) in healthcare facilities that were not Ebola treatment units, as well as to IPC trainers and IPC supervisors placed in healthcare facilities. Trainings included both didactic and hands-on components, and were assessed using pre-tests, post-tests and practical evaluations. We calculated median percent increase in knowledge. Results From October–December 2014, 20 IPC courses trained 1,625 Guineans: 1,521 HCW, 55 IPC trainers, and 49 IPC supervisors. Median test scores increased 40% (interquartile range [IQR]: 19–86%) among HCW, 15% (IQR: 8–33%) among IPC trainers, and 21% (IQR: 15–30%) among IPC supervisors (all P

In 2014, as part of the Global Health Security Agenda, Ethiopia was provided the technical and financial resources needed to prioritize antimicrobial resistance (AMR) in the national public health sphere. Under the direction of a multi-stakeholder working group, AMR surveillance was launched in July 2017 at 4 sentinel sites across the country. The AMR surveillance initiative in Ethiopia represents one of the first systematic efforts to prospectively collect, analyze, and report national-level microbiology results from a network of hospitals and public health laboratories in the country. Baseline readiness assessments were conducted to identify potential challenges to implementation to be addressed through capacity-building efforts. As part of these efforts, the working group leveraged existing resources, initiated laboratory capacity building through mentorship, and established infrastructure and systems for quality assurance, data management, and improved coordination. As a result, AMR surveillance data are being reported and analyzed for use; data from more than 1,700 patients were collected between July 2017 and March 2018. The critical challenges and effective solutions identified through surveillance planning and implementation have provided lessons to help guide successful AMR surveillance in other settings. Ultimately, the surveillance infrastructure, laboratory expertise, and communication frameworks built specifically for AMR surveillance in Ethiopia can be extended for use with other infectious diseases and potential public health emergencies. Thus, building AMR surveillance in Ethiopia has illustrated how laying the foundation for a specific public health initiative can develop capacity for core public health functions with potential benefit.

Coccidioidomycosis (CM), a serious life-threatening fungal infection endemic to arid regions of the western United States and Mexico, can be challenging to diagnose in a timely manner. Commercially developed enzyme immunoassays (EIAs) (from Meridian Biosciences and Immuno-Mycologics [IMMY]) have provided faster, simpler means for serodiagnosis; however, independent evaluations have questioned EIA specificity, particularly IgM-positive/IgG-negative results. This study was conducted to evaluate EIA specificity among persons residing in Puerto Rico ( n = 534), where CM is not endemic (who were not likely to have been exposed to Coccidioides spp.), compared to blood bank donors residing in Arizona ( n = 1,218), where CM is endemic. Upon comparing serum reactivity between Puerto Rico and Arizona, the Meridian EIA showed a significant difference in IgG reactivity (0.37% versus 3.6%; P < 0.001) but not IgM reactivity (3.4% versus 2.4%; P = 0.31). No IgM-/IgG-reactive sera were detected among sera from Puerto Rico, compared to 7 (0.57%) sera from Arizona. Similar results were observed using the IMMY EIA, although significantly ( P = 0.03) fewer IgM-reactive sera from Arizona were observed, compared to the Meridian EIA. EIA-reactive sera were also evaluated by immunodiffusion before and after 3- to 4-fold concentration of the sera. These results demonstrate that elevated IgG EIA reactivity is present in sera from healthy individuals in regions of endemicity and that IgM EIA reactivity observed in sera from individuals residing outside regions of endemicity is most likely nonspecific. Other criteria, including clinical and microbiological evaluations, should be taken into account when interpreting results from surveillance studies and other reporting measures.

Public health response to the outbreak likely resulted fewer injections, cases, and deaths. Deaths, Illnesses Averted in Meningitis Outbreak, During 2012–2013, the US Centers for Disease Control and Prevention and partners responded to a multistate outbreak of fungal infections linked to methylprednisolone acetate (MPA) injections produced by a compounding pharmacy. We evaluated the effects of public health actions on the scope of this outbreak. A comparison of 60-day case-fatality rates and clinical characteristics of patients given a diagnosis on or before October 4, the date the outbreak was widely publicized, with those of patients given a diagnosis after October 4 showed that an estimated 3,150 MPA injections, 153 cases of meningitis or stroke, and 124 deaths were averted. Compared with diagnosis after October 4, diagnosis on or before October 4 was significantly associated with a higher 60-day case-fatality rate (28% vs. 5%; p

Measles virus is highly infectious and can spread rapidly where vaccine coverage is low and isolation precautions suboptimal. We describe healthcare-associated measles transmission during the 2015-2016 measles outbreak in Mongolia, describe infection prevention gaps, and outline preventive strategies.

Summary Background Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease. Methods We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis. Findings We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8–6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500–340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600–282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600–193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400–234 300), with 135 900 (75%; [95% CI 93 900–163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10–19). Interpretation Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority. Funding None.

Candida glabrata is the second leading cause of candidemia in U.S. hospitals. Current guidelines suggest that an echinocandin be used as the primary therapy for the treatment of C. glabrata disease due to the high rate of resistance to fluconazole. Recent case reports indicate that C. glabrata resistance to echinocandins may be increasing. We performed susceptibility testing on 1,380 isolates of C. glabrata collected between 2008 and 2013 from four U.S. cities, Atlanta, Baltimore, Knoxville, and Portland. Our analysis showed that 3.1%, 3.3%, and 3.6% of the isolates were resistant to anidulafungin, caspofungin, and micafungin, respectively. We screened 1,032 of these isolates, including all 77 that had either a resistant or intermediate MIC value with respect to at least one echinocandin, for mutations in the hot spot regions of FKS1 and FKS2 , the major mechanism of echinocandin resistance. Fifty-one isolates were identified with hot spot mutations, 16 in FKS1 and 35 in FKS2 . All of the isolates with an FKS mutation except one were resistant to at least one echinocandin by susceptibility testing. Of the isolates resistant to at least one echinocandin, 36% were also resistant to fluconazole. Echinocandin resistance among U.S. C. glabrata isolates is a concern, especially in light of the fact that one-third of those isolates may be multidrug resistant. Further monitoring of U.S. C. glabrata isolates for echinocandin resistance is warranted.

Fungal endophthalmitis is a rare but serious infection. In March 2012, several cases of probable and laboratory-confirmed fungal endophthalmitis occurring after invasive ocular procedures were reported nationwide. We identified 47 cases in 9 states: 21 patients had been exposed to the intraocular dye Brilliant Blue G (BBG) during retinal surgery, and the other 26 had received an intravitreal injection containing triamcinolone acetonide. Both drugs were produced by Franck’s Compounding Lab (Ocala, FL, USA). Fusarium incarnatum-equiseti species complex mold was identified in specimens from BBG-exposed case-patients and an unopened BBG vial. Bipolaris hawaiiensis mold was identified in specimens from triamcinolone-exposed case-patients. Exposure to either product was the only factor associated with case status. Of 40 case-patients for whom data were available, 39 (98%) lost vision. These concurrent outbreaks, associated with 1 compounding pharmacy, resulted in a product recall. Ensuring safety and integrity of compounded medications is critical for preventing further outbreaks associated with compounded products. Download MP3 Length: 1:42

Since September 2012, the Centers for Disease Control and Prevention (CDC), together with state and local health departments, has been investigating an outbreak of fungal meningitis and other infections associated with injection of contaminated methylprednisolone acetate (MPA) produced by the New England Compounding Center (NECC). By October 2013, 751 cases were identified with 64 deaths, making this one of the largest recorded healthcare-associated outbreaks in US history [1, 2]. Although several molds were isolated from cerebrospinal fluid (CSF) and tissues of case patients, Exserohilum rostratum has been the predominant pathogen [3, 4]. Invasive infection due to E. rostratum, a fungus found in soil associated with plants [5], is rare and has previously been described only in persons with impaired immune systems [6, 7]. Furthermore, until this outbreak no cases of meningitis or encephalitis caused by this fungus had been reported. As part of the response to this public health disaster, the CDC developed a rapid polymerase chain reaction (PCR) test for detection of fungal DNA in human fluids and tissues [8]. This assay is estimated to have 29% diagnostic sensitivity and 100% specificity. (1,3)-β-d-glucan (BDG) is a glucose polymer that is part of the fungal cell wall [9]. The Fungitell assay (Associates of Cape Cod, Inc, Falmouth, Massachusetts) has been approved by the US Food and Drug Administration (FDA) for detection of BDG in human serum and used in diagnosis of fungal infections [10–12]. The potential drawbacks of this assay include (1) inability to differentiate among fungal species causing infections, (2) cross-reactivity with certain bacteria and drugs, and (3) false positivity due to specimen contamination [10]. Therefore, results of this assay must be interpreted in combination with clinical and epidemiological findings. There are few data on the Fungitell assay using CSF in patients with fungal meningitis [13, 14]; one recent report using this assay in 5 patients from this outbreak demonstrated that 3 had elevated CSF levels of BDG [15]. Here, we explore BDG as a supplemental diagnostic marker for fungal meningitis in this outbreak, and assess its utility for evaluating patients' response to treatment.

Fungal infections are rare complications of injections for treatment of chronic pain. In September 2012, we initiated an investigation into fungal infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy.Three lots of methylprednisolone acetate were recalled by the pharmacy; examination of unopened vials later revealed fungus. Notification of all persons potentially exposed to implicated methylprednisolone acetate was conducted by federal, state, and local public health officials and by staff at clinical facilities that administered the drug. We collected clinical data on standardized case-report forms, and we tested for the presence of fungi in isolates and specimens by examining cultures and performing polymerase-chain-reaction assays and histopathological and immunohistochemical testing.By October 19, 2012, more than 99% of 13,534 potentially exposed persons had been contacted. As of July 1, 2013, there were 749 reported cases of infection in 20 states, with 61 deaths (8%). Laboratory evidence of Exserohilum rostratum was present in specimens from 153 case patients (20%). Additional data were available for 728 case patients (97%); 229 of these patients (31%) had meningitis with no other documented infection. Case patients had received a median of 1 injection (range, 1 to 6) of implicated methylprednisolone acetate. The median age of the patients was 64 years (range, 15 to 97), and the median incubation period (the number of days from the last injection to the date of the first diagnosis) was 47 days (range, 0 to 249); 40 patients (5%) had a stroke.Analysis of data from a large, multistate outbreak of fungal infections showed substantial morbidity and mortality. The infections were associated with injection of a contaminated glucocorticoid medication from a single compounding pharmacy. Rapid public health actions included prompt recall of the implicated product, notification of exposed persons, and early outreach to clinicians.

Clonal VGII subtypes (outbreak strains) of Cryptococcus gattii have caused an outbreak in the US Pacific Northwest since 2004. Outbreak-associated infections occur equally in male and female patients (median age 56 years) and usually cause pulmonary disease in persons with underlying medical conditions. Since 2009, a total of 25 C. gattii infections, 23 (92%) caused by non–outbreak strain C. gattii, have been reported from 8 non–Pacific Northwest states. Sixteen (64%) patients were previously healthy, and 21 (84%) were male; median age was 43 years (range 15–83 years). Ten patients who provided information reported no past-year travel to areas where C. gattii is known to be endemic. Nineteen (76%) patients had central nervous system infections; 6 (24%) died. C. gattii infection in persons without exposure to known disease-endemic areas suggests possible endemicity in the United States outside the outbreak-affected region; these infections appear to differ in clinical and demographic characteristics from outbreak-associated C. gattii. Clinicians outside the outbreak-affected areas should be aware of locally acquired C. gattii infection and its varied signs and symptoms.

Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count 3. Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia.

Objective.To quantify historical trends in rates of central line-associated bloodstream infections (CLABSIs) in US intensive care units (ICUs) caused by major pathogen groups, includingCandidaspp.,Enterococcusspp., specified gram-negative rods, andStaphylococcus aureus.Design.Active surveillance in a cohort of participating ICUs through the Centers for Disease Control and Prevention, the National Nosocomial Infections Surveillance system during 1990–2004, and the National Healthcare Safety Network during 2006–2010.Setting.ICUS.Participants.Patients who were admitted to participating ICUs.Results.The CLABSI incidence density rate forS. aureusdecreased annually starting in 2002 and remained lower than for other pathogen groups. Since 2006, the annual decrease forS. aureusCLABSIs in nonpediatric ICU types was −18.3% (95% confidence interval [CI], −20.8% to −15.8%), whereas the incidence density rate forS. aureusamong pediatric ICUs did not change. The annual decrease for all ICUs combined since 2006 was −17.8% (95% CI, −19.4% to −16.1%) forEnterococcusspp., −16.4% (95% CI, −18.2% to −14.7%) for gram-negative rods, and −13.5% (95% CI, −15.4% to −11.5%) forCandidaspp.Conclusions.Patterns of ICU CLABSI incidence density rates among major pathogen groups have changed considerably during recent decades. CLABSI incidence declined steeply since 2006, except for CLABSI due toS. aureusin pediatric ICUs. There is a need to better understand CLABSIs that still do occur, on the basis of microbiological and patient characteristics. New prevention approaches may be needed in addition to central line insertion and maintenance practices.

Background. Blastomycosis is a potentially life-threatening infection caused by the soil-based dimorphic fungus Blastomyces dermatitidis, which is endemic throughout much of the Midwestern United States. We investigated an increase in reported cases of blastomycosis that occurred during 2009–2010 in Marathon County, Wisconsin. Methods. Case detection was conducted using the Wisconsin Electronic Disease Surveillance System (WEDSS). WEDSS data were used to compare demographic, clinical, and exposure characteristics between outbreak-related and historical case patients, and to calculate blastomycosis incidence rates. Because initial mapping of outbreak case patients’ homes and recreational sites demonstrated unusual neighborhood and household case clustering, we conducted a 1:3 matched case-control study to identify factors associated with being in a geographic cluster. Results. Among the 55 patients with outbreak-related cases, 33 (70%) were hospitalized, 2 (5%) died, 30 (55%) had cluster-related cases, and 20 (45%) were Hmong. The overall incidence increased significantly since 2005 (average 11% increase per year, P< .001), and incidence during 2005–2010 was significantly higher among Asians than non-Asians (2010 incidence: 168 vs 13 per 100 000 population). Thirty of the outbreak cases grouped into 5 residential clusters. Outdoor activities were not risk factors for blastomycosis among cluster case patients or when comparing outbreak cases to historical cases. Conclusions. This outbreak of blastomycosis, the largest ever reported, was characterized by unique household and neighborhood clustering likely related to multifocal environmental sources. The reasons for the large number of Hmong affected are unclear, but may involve genetic predisposition.

We investigated an increase in Trichosporon asahii isolates among inpatients. We identified 63 cases; 4 involved disseminated disease. Trichosporon species was recovered from equipment cleaning rooms, washbasins, and fomites, which suggests transmission through washbasins. Patient washbasins should be single-patient use only; adherence to appropriate hospital disinfection guidelines was recommended.