BACKGROUND: In Malawi approximately, 88.3% people living with HIV are aware of their HIV status. Significant gaps are among men aged 15-34 years; only 72% know their HIV status. To reach men, Jhpiego, in collaboration with the Ministry of Health (MOH), implemented the Men's Mobile Wellness Clinic (MMWC) at workplace settings in Blantyre, Malawi between October 2019 and March 2020. METHODS: We conducted a descriptive qualitative study to understand motivators and barriers to MMWC service uptake by employees and employers. Primary data was drawn from in-depth telephone interviews from four study populations: employers who accepted or declined to host the MMWC at their worksite, and employees who accessed or did not access the services. We performed a thematic analysis using Nvivo 12 software to identify patterns and themes across the dataset. FINDINGS: Main reasons given for using the service among male employees were a desire to know their health status, availability of free health services at the workplace, and good quality services offered by MMWC staff, and support from their supervisor. Men who did not access services stated reasons such as work-clinic scheduling conflicts, lack of adequate promotion of the service, and miscommunication on the criteria about who should attend the MMWC. Employers who accepted to host the MMWC stated convenience and employee's rights to know their health status. Those who declined either stated that employees did not want the services or COVID-19 preventive measures by the MOH between October 2019 and March 2020 restricted participation. CONCLUSION: This study underscores the potential utility of MMWC services including HIV testing among men. The desire to know their health status, availability of free MMWC services at the workplace, good quality services offered by MMWC staff, and the endorsement of MMWC by supervisors were main motivators to access the MMWC services. Sensitizing supervisors and employees about the benefits of the MMWC services, strengthening demand creation, and clarifying eligibility are important to facilitate MMWC uptake among men in Malawi.

Author summary  • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.  • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing.  • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions.  • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality in U.S. nursing homes (1); however, reduced effectiveness of monovalent vaccines during the period of Omicron variant predominance led to recommendations for booster doses with bivalent COVID-19 mRNA vaccines that include an Omicron BA.4/BA.5 spike protein component to broaden immune response and improve vaccine effectiveness against circulating Omicron variants (2). Recent studies suggest that bivalent booster doses provide substantial additional protection against SARS-CoV-2 infection and severe COVID-19-associated disease among immunocompetent adults who previously received only monovalent vaccines (3).* The immunologic response after receipt of bivalent boosters among nursing home residents, who often mount poor immunologic responses to vaccines, remains unknown. Serial testing of anti-spike protein antibody binding and neutralizing antibody titers in serum collected from 233 long-stay nursing home residents from the time of their primary vaccination series and including any subsequent booster doses, including the bivalent vaccine, was performed. The bivalent COVID-19 mRNA vaccine substantially increased anti-spike and neutralizing antibody titers against Omicron sublineages, including BA.1 and BA.4/BA.5, irrespective of previous SARS-CoV-2 infection or previous receipt of 1 or 2 booster doses. These data, in combination with evidence of low uptake of bivalent booster vaccination among residents and staff members in nursing homes (4), support the recommendation that nursing home residents and staff members receive a bivalent COVID-19 booster dose to reduce associated morbidity and mortality (2).

BACKGROUND: In 2012, the US Department of Health and Human Services updated their HIV treatment guidelines to recommend antiretroviral therapy (ART) for all people with HIV (PWH) regardless of CD4 count. We investigated recent trends and disparities in early receipt of ART prescription and subsequent viral suppression (VS). METHODS: We examined data from ART-naïve PWH newly presenting to HIV care at 13 North American AIDS Cohort Collaboration on Research and Design clinical cohorts in the United States during 2012-2018. We calculated the cumulative incidence of early ART (within 30 days of entry into care) and early VS (within 6 months of ART initiation) using the Kaplan-Meier survival function. Discrete time-to-event models were fit to estimate unadjusted and adjusted associations of early ART and VS with sociodemographic and clinical factors. RESULTS: Among 11 853 eligible ART-naïve PWH, the cumulative incidence of early ART increased from 42% in 2012 to 82% in 2018. The cumulative incidence of early VS among the 8613 PWH who initiated ART increased from 83% in 2012 to 93% in 2018. In multivariable models, factors independently associated with delayed ART and VS included non-Hispanic/Latino Black race, residence in the South census region, being a male with injection drug use acquisition risk, and history of substance use disorder (SUD; all P ≤ .05). CONCLUSIONS: Early ART initiation and VS have substantially improved in the United States since the release of universal treatment guidelines. Disparities by factors related to social determinants of health and SUD demand focused attention on and services for some subpopulations.

The codon usage and dinucleotide frequencies of an organism depend mostly on its nucleotide composition, but also on the evolutionary forces that have acted on its genome including mutation, genetic drift, and selection. Different selection pressures may contribute to shape the genome composition and codon usage of viruses: | | - Codon usage and dinucleotide biases may result from the need to maintain RNA secondary structures involved in splicing and gene expression (Takata et al., 2018). | - Dinucleotide bias may result from the need to evade cell defense mechanisms. UpA, and particularly CpG, dinucleotides may be perceived as pathogen-associated molecular patterns by host cells and consequently their frequencies in viral genomes tend to decrease (Atkinson et al., 2014). | - Codon usage may also result from translation selection. Abundant codons, pairing with abundant tRNAs, would be selected over rare codons, pairing with non-abundant tRNAs, to improve the efficiency and accuracy of translation. On the contrary, rare codons would persist through mutational pressure and genetic drift (Duret, 2002; Hershberg and Petrov, 2008). Viruses do not code for tRNAs, and instead they use the host tRNA pool for their own translation, making even harder to discern the role of selection on shaping their codon usage. Although a similar codon usage between viruses and their hosts may be anticipated, excessive similarity may impede host translation, with the associated deleterious effects; consequently, viruses have evolved to an optimal range of codon usage bias (Moratorio et al., 2013; Chen et al., 2020). | - Codon usage may also be shaped by selection for the control of the translation rate. The scarcity of rare codon pairing tRNAs may result in ribosome stalling, slowing down the mRNA translation speed. In doing so, rare codons may play a role in controlling the co-translational folding (Chaney and Clark, 2015; Yu et al., 2015; Zhao et al., 2017; D'Andrea et al., 2019; Pintó and Bosch, 2021). | - Additionally, codon usage may be selected to maintain mutational robustness. Codons one mutation apart from a stop codon may tend to be avoided in genomes (Moratorio et al., 2017; Carrau et al., 2019).

BACKGROUND: Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general population. OBJECTIVE: To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time. DESIGN: Observational cohort study. SETTING: Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design. PARTICIPANTS: 82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics. MEASUREMENTS: Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function. RESULTS: Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017. LIMITATION: Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors. CONCLUSION: Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population. PRIMARY FUNDING SOURCE: National Institutes of Health.

BACKGROUND: To assess the possible impact of antiretroviral therapy improvements, aging, and comorbidities, we examined trends in all-cause and cause-specific hospitalization rates among persons with HIV (PWH) from 2005 to 2015. METHODS: In six clinical cohorts, we followed PWH in care (≥1 outpatient CD4 count or HIV viral load [VL] every 12 months) and categorized ICD codes of primary discharge diagnoses using modified Clinical Classifications Software. Poisson regression estimated hospitalization rate ratios for calendar time trends, adjusted for demographics, HIV risk factor, and annually-updated age, CD4, and VL. RESULTS: Among 28 057 patients (125 724 person-years), from 2005 to 2015, the median CD4 increased from 389 to 580 cells/µL and virologic suppression from 55% to 85% of patients. Unadjusted all-cause hospitalization rates decreased from 22.3 per 100 person-years in 2005 (95% CI 20.6-24.1) to 13.0 in 2015 (12.2-14.0). Unadjusted rates decreased for almost all diagnostic categories. Adjusted rates decreased for all-cause, cardiovascular, and AIDS-defining conditions, increased for non-AIDS-defining infection, and were stable for most other categories. CONCLUSIONS: Among PWH with increasing CD4 counts and viral suppression, unadjusted hospitalization rates decreased for all-cause and most cause-specific hospitalizations, despite the potential effects of aging, comorbidities, and cumulative exposure to HIV and antiretrovirals.

BACKGROUND: Persons living with HIV (PLWH) experience a high burden of cancer. It remains unknown which cancer types are reduced in PLWH with earlier initiation of antiretroviral therapy (ART). METHODS: We evaluated AIDS-free, ART-naive PLWH during 1996-2014 from 22 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. PLWH were followed from first observed CD4 of 350-500 cells/µl (baseline) until incident cancer, death, lost-to-follow-up or December 2014. Outcomes included six cancer groups and five individual cancers that were confirmed by chart review or cancer registry linkage. We evaluated the effect of earlier (in the first 6 months after baseline) versus deferred ART initiation on cancer risk. Marginal structural models were used with inverse probability weighting to account for time-dependent confounding and informative right-censoring, with weights informed by subject's age, sex, cohort, baseline year, race/ethnicity, HIV transmission risk, smoking, viral hepatitis, CD4, and AIDS diagnoses. RESULTS: Protective results for earlier ART were found for any cancer (adjusted hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.37-0.86), AIDS-defining cancers (HR 0.23; 95% CI 0.11-0.49), any virus-related cancer (HR 0.30; 95% CI 0.16-0.54), Kaposi sarcoma (HR 0.25; 95% CI 0.10-0.61) and non-Hodgkin lymphoma (HR 0.22; 95% CI 0.06-0.73). By 15 years, there was also an observed reduced risk with earlier ART for virus-related NADCs (0.6% vs. 2.3%; adjusted risk difference -1.6; 95% CI -2.8, -0.5). CONCLUSIONS: Earlier ART initiation has potential to reduce the burden of virus-related cancers in PLWH, but not NADCs without known or suspected viral etiology.

Background Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. Methods We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. Results There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts <100 cells/mm 3. PAFs for NADCs increased during 1995-2009, reaching 10.1% in 2006-2009. Conclusions Approximately 10% of deaths in PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this fraction increased over time. A large proportion of cancer-attributable deaths were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV age.

BACKGROUND: Understanding the flow of patients through the continuum of HIV care is critical to determine how best to intervene so that the proportion of HIV-infected persons who are on antiretroviral treatment and virally suppressed is as large as possible. METHODS: Using immunological and virological data from the Centers for Disease Control and Prevention and the North American AIDS Cohort Collaboration on Research and Design from 2009 to 2012, we estimated the distribution of time spent in and dropout probability from each stage in the continuum of HIV care. We used these estimates to develop a queueing model for the expected number of patients found in each stage of the cascade. RESULTS: HIV-infected individuals spend an average of about 3.1 months after HIV diagnosis before being linked to care, or dropping out of that stage of the continuum with a probability of 8%. Those who link to care wait an additional 3.7 months on average before getting their second set of laboratory results (indicating engagement in care) or dropping out of care with probability of almost 6%. Those engaged in care spent an average of almost 1 year before achieving viral suppression on antiretroviral therapy or dropping out with average probability 13%. For patients who achieved viral suppression, the average time suppressed on antiretroviral therapy was an average of 4.5 years. CONCLUSIONS: Interventions should be targeted to more rapidly identifying newly infected individuals, and increasing the fraction of those engaged in care that achieves viral suppression.

BACKGROUND: There remains concern regarding the occurrence of non-communicable diseases (NCDs) among individuals aging with HIV but few studies have described whether disparities between demographic subgroups are present among individuals on antiretroviral therapy (ART) with access to care. METHODS: We assessed the first documented occurrence of type 2 diabetes mellitus (DM), chronic kidney disease (CKD), and treated hypertension (HTN) by age, sex, and race within the North American AIDS Cohort Collaboration on Research and Design. HIV-infected adults (≥18 years) who initiated ART were observed for first NCD occurrence between 1 January 2000 - 31 December 2013. Cumulative incidences as of age 70 were estimated accounting for the competing risk of death; Poisson regression was used to compare rates of NCD occurrence by demographic subgroup. RESULTS: We included >50,000 persons with >250,000 person-years (PY) of follow-up. Median follow-up was 4.7 years (interquartile range (IQR): 2.4-8.1). Rates of first occurrence (per 100 PY) were: 1.2 for DM, 0.6 for CKD, and 2.6 for HTN. Relative to non-black women, the cumulative incidences were increased in black women (68% vs. 51% for HTN, 52% vs. 41% for DM, and 38% vs. 35% for CKD; all p<0.001); this disparity was also found among men (73% vs. 60% for HTN, 44% vs. 34% for DM, and 30% vs. 25% for CKD; all p<0.001). CONCLUSIONS: Racial disparities in the occurrence of DM, CKD, and HTN emphasize the need for prevention and treatment options for these HIV populations receiving care in North America.

BACKGROUND: Epi-Aids, or epidemiologic assistance investigations, are an important mechanism through which Centers for Disease Control and Prevention supports public health organizations. We described the characteristics of Epi-Aids conducted during 2005-2014 and summarized the publication outcome of Epi-Aid related scientific information products. METHODS: We performed a descriptive analysis of all Epi-Aids conducted during January 1, 2005-December 31, 2014; investigations were categorized by health topic and geographic distribution. We highlighted investigations of substantial public health importance, e.g., multistate investigations and investigations of epidemics and pandemics. We identified the Epi-Aid publication outcome by searching PubMed for Epi-Aid related publications, which included Morbidity and Mortality Weekly Reports (MMWRs) and peer-reviewed publications with an Epidemic Intelligence Service Officer (EISO) as a coauthor. We calculated publication timeliness and categorized publications by journal impact factor. RESULTS: During the study period, 698 EISOs and their collaborators participated in 807 Epi-Aids throughout the United States and globally. Approximately 81 Epi-Aids were conducted annually (range, 62-104); 632 (78.3%) were infectious disease-related; 161 (20.0%) were international, supporting 68 countries. As of June 2015, EISOs, in collaboration with partners, published 131 MMWRs and 280 scientific manuscripts on the basis of the 807 Epi-Aids conducted during the study period; 394 (48.8%) Epi-Aids resulted in publications in 80 peer-reviewed journals. CONCLUSIONS: EISOs play a critical role in conducting Epi-Aids, which require qualified field epidemiologists who can rapidly respond to requests for assistance during public health emergencies. Publications based on Epi-Aids share new knowledge with the scientific community, furthering progress of public health science and practice.

BACKGROUND: There are few recent data on the rates of AIDS-defining opportunistic infections (OIs) among human immunodeficiency virus (HIV)-infected patients in care in the United States and Canada. METHODS: We studied HIV-infected participants in 16 cohorts in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) during 2000-2010. After excluding 16 737 (21%) with any AIDS-defining clinical events documented before NA-ACCORD enrollment, we analyzed incident OIs among the remaining 63 541 persons, most of whom received antiretroviral therapy during the observation. We calculated incidence rates per 100 person-years of observation (hereafter, "person-years") with 95% confidence intervals (CIs) for the first occurrence of any OI and select individual OIs during 2000-2003, 2004-2007, and 2008-2010. RESULTS: A total of 63 541 persons contributed 261 573 person-years, of whom 5836 (9%) developed at least 1 OI. The incidence rate of any first OI decreased over the 3 observation periods, with 3.0 cases, 2.4 cases, and 1.5 cases per 100 person-years of observation during 2000-2003, 2004-2007, and 2008-2010, respectively (Ptrend<.001); the rates of most individual OIs decreased as well. During 2008-2010, the leading OIs included Pneumocystis jiroveci pneumonia, esophageal candidiasis, and disseminated Mycobacterium avium complex or Mycobacterium kansasii infection. CONCLUSIONS: For HIV-infected persons in care during 2000-2010, rates of first OI were relatively low and generally declined over this time.

During 2006-2014, a total of 15 multistate outbreaks of turtle-associated salmonellosis in humans were reported in the United States. Exposure to small pet turtles has long been recognized as a source of human salmonellosis. The risk to public health has persisted and may be increasing. Turtles are a popular reptilian pet among children, and numerous risky behaviors for the zoonotic transmission of Salmonella bacteria to children have been reported in recent outbreaks. Despite a long-standing federal ban against the sale and distribution of turtles <4 in (<10.16 cm) long, these small reptiles can be readily acquired through multiple venues and continue to be the main source of turtle-associated salmonellosis in children. Enhanced efforts are needed to minimize the disease risk associated with small turtle exposure. Prevention will require novel partnerships and a comprehensive One Health approach involving human, animal, and environmental health.

OBJECTIVE: Turtle-associated salmonellosis (TAS), especially in children, is a reemerging public health issue. In 1975, small pet turtles (shell length <4 inches) sales were banned by federal law; reductions in pediatric TAS followed. Since 2006, the number of multistate TAS outbreaks has increased. We describe 8 multistate outbreaks with illness-onset dates occurring in 2011-2013. METHODS: We conducted epidemiologic, environmental, and traceback investigations. Cases were defined as infection with ≥1 of 10 molecular subtypes of Salmonella Sandiego, Pomona, Poona, Typhimurium, and I 4,[5],12:i:-. Water samples from turtle habitats linked to human illnesses were cultured for Salmonella. RESULTS: We identified 8 outbreaks totaling 473 cases from 41 states, Washington DC, and Puerto Rico with illness onsets during May 2011-September 2013. The median patient age was 4 years (range: 1 month-94 years); 45% percent were Hispanic; and 28% were hospitalized. In the week preceding illness, 68% (187 of 273) of case-patients reported turtle exposure; among these, 88% (124 of 141) described small turtles. Outbreak strains were isolated from turtle habitats linked to human illnesses in seven outbreaks. Traceback investigations identified 2 Louisiana turtle farms as the source of small turtles linked to 1 outbreak; 1 outbreak strain was isolated from turtle pond water from 1 turtle farm. CONCLUSIONS: Eight multistate outbreaks associated with small turtles were investigated during 2011-2013. Children <5 years and Hispanics were disproportionately affected. Prevention efforts should focus on patient education targeting families with young children and Hispanics and enactment of state and local regulations to complement federal sales restrictions.

In May 2014, a cluster of human Salmonella Poona infections was identified through PulseNet, the national molecular subtyping network for foodborne disease surveillance. Historically, this rare serotype has been identified in multiple Salmonella outbreaks associated with pet turtle exposure and has posed a particular risk to small children. Although the sale and distribution of small turtles (those with carapace [upper shell] lengths <4 inches [<10.2 cm]) is prohibited by federal law, they are still available for legal purchase online for "bona-fide" scientific, educational, or exhibition purposes, other than use as pets. In addition, small turtles are still available for illegal purchase through transient street vendors, at flea markets, and at fairs.

The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an international collaboration of public health institutes and universities which has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2012. Main objective is to define a framework for evaluating and grading evidence in the field of public health, with particular focus on infectious disease prevention and control. As part of the peer review process, an international expert meeting was held on 13-14 June 2013 in Berlin. Participants were members of the PRECEPT team and selected experts from national public health institutes, World Health Organization (WHO), and academic institutions. The aim of the meeting was to discuss the draft framework and its application to two examples from infectious disease prevention and control. This article introduces the draft PRECEPT framework and reports on the meeting, its structure, most relevant discussions and major conclusions.

On 23 May 2011, CDC identified a multistate cluster of Salmonella Heidelberg infections and two multidrug-resistant (MDR) isolates from ground turkey retail samples with indistinguishable pulsed-field gel electrophoresis patterns. We defined cases as isolation of outbreak strains in persons with illness onset between 27 February 2011 and 10 November 2011. Investigators collected hypothesis-generating questionnaires and shopper-card information. Food samples from homes and retail outlets were collected and cultured. We identified 136 cases of S. Heidelberg infection in 34 states. Shopper-card information, leftover ground turkey from a patient's home containing the outbreak strain and identical antimicrobial resistance profiles of clinical and retail samples pointed to plant A as the source. On 3 August, plant A recalled 36 million pounds of ground turkey. This outbreak increased consumer interest in MDR Salmonella infections acquired through United States-produced poultry and played a vital role in strengthening food safety policies related to Salmonella and raw ground poultry.

The 2013 multistate outbreaks contributed to the largest annual number of reported US cases of cyclosporiasis since 1997. In this paper we focus on investigations in Texas. We defined an outbreak-associated case as laboratory-confirmed cyclosporiasis in a person with illness onset between 1 June and 31 August 2013, with no history of international travel in the previous 14 days. Epidemiological, environmental, and traceback investigations were conducted. Of the 631 cases reported in the multistate outbreaks, Texas reported the greatest number of cases, 270 (43%). More than 70 clusters were identified in Texas, four of which were further investigated. One restaurant-associated cluster of 25 case-patients was selected for a case-control study. Consumption of cilantro was most strongly associated with illness on meal date-matched analysis (matched odds ratio 19.8, 95% confidence interval 4.0-infinity). All case-patients in the other three clusters investigated also ate cilantro. Traceback investigations converged on three suppliers in Puebla, Mexico. Cilantro was the vehicle of infection in the four clusters investigated; the temporal association of these clusters with the large overall increase in cyclosporiasis cases in Texas suggests cilantro was the vehicle of infection for many other cases. However, the paucity of epidemiological and traceback information does not allow for a conclusive determination; moreover, molecular epidemiological tools for cyclosporiasis that could provide more definitive linkage between case clusters are needed.

BACKGROUND: Pneumonia and diarrhea are leading causes of death for children under five (U5). It is challenging to estimate the total number of deaths and cause-specific mortality fractions. Two major efforts, one led by the Institute for Health Metrics and Evaluation (IHME) and the other led by the World Health Organization (WHO)/Child Health Epidemiology Reference Group (CHERG) created estimates for the burden of disease due to these two syndromes, yet their estimates differed greatly for 2010. METHODS: This paper discusses three main drivers of the differences: data sources, data processing, and covariates used for modelling. The paper discusses differences in the model assumptions for etiology-specific estimates and presents recommendations for improving future models. RESULTS: IHME inverted question marks Global Burden of Disease (GBD) 2010 study estimated 6.8 million U5 deaths compared to 7.6 million U5 deaths from CHERG. The proportional differences between the pneumonia and diarrhea burden estimates from the two groups are much larger; GBD 2010 estimated 0.847 million and CHERG estimated 1.396 million due to pneumonia. Compared to CHERG, GBD 2010 used broader inclusion criteria for verbal autopsy and vital registration data. GBD 2010 and CHERG used different data processing procedures and therefore attributed the causes of neonatal death differently. The major difference in pneumonia etiologies modeling approach was the inclusion of observational study data; GBD 2010 included observational studies. CHERG relied on vaccine efficacy studies. DISCUSSION: Greater transparency in modeling methods and more timely access to data sources are needed. In October 2013, the Bill & Melinda Gates Foundation (BMGF) hosted an expert meeting to examine possible approaches for better estimation. The group recommended examining the impact of data by systematically excluding sources in their models. GBD 2.0 will use a counterfactual approach for estimating mortality from pathogens due to specific etiologies to overcome bias of the methods used in GBD 2010 going forward.

In early 2014, five clusters of human Salmonella infections were identified through PulseNet, the national molecular subtyping network for foodborne disease surveillance. Many ill persons in each of these clusters reported contact with live poultry, primarily chicks and ducklings, from a single mail-order hatchery; therefore, the clusters were merged into a single investigation. During February 3-October 14, 2014, a total of 363 persons infected with outbreak strains of Salmonella serotypes Infantis, Newport, and Hadar were reported from 43 states and Puerto Rico, making it the largest live poultry-associated salmonellosis outbreak reported in the United States.

Salmonella spp. cause ≈1.2 million human illnesses annually in the United States (1). Infections are primarily acquired through exposure to contaminated food or infected animals (1,2). Since 2007, state and local health departments and the Centers for Disease Control and Prevention have investigated multiple salmonellosis outbreaks linked to meat purchased at live-bird markets (LBMs) and live-animal markets (LAMs), where poultry and livestock are sold for onsite slaughter. These markets typically operate in large cities and serve populations of diverse ethnic backgrounds (3). | | In 2007, an outbreak involving 62 case-patients infected with 1 of 3 S. enterica serotype Schwarzengrund strains was investigated in Massachusetts; 61% were children <5 years of age, including 14 (23%) infants <1 year of age, and 96% were Asian (Table). A case-patient was defined as a person infected with S. enterica who had a pulsed-field gel electrophoresis XbaI restriction enzyme pattern indistinguishable from the outbreak strain. Exposure to poultry purchased at LBMs was reported, and environmental sampling at an implicated LBM identified 6 S. enterica serotypes, including 1 outbreak strain.

On June 27, 2013, the Minnesota Department of Health notified CDC of two patients with invasive Listeria monocytogenes infections (listeriosis) whose clinical isolates had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. A query of PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified clinical and environmental isolates from other states. On June 28, CDC learned from the Food and Drug Administration's Coordinated Outbreak Response and Evaluation Network that environmental isolates indistinguishable from those of the two patients had been collected from Crave Brothers Farmstead Cheese during 2010-2011. An outbreak-related case was defined as isolation of L. monocytogenes with the outbreak PFGE pattern from an anatomic site that is normally sterile (e.g., blood or cerebrospinal fluid), or from a product of conception, with an isolate upload date during May 20-June 28, 2013. As of June 28, five cases were identified in four states (Minnesota, two cases; Illinois, Indiana, and Ohio, one each). Median age of the five patients was 58 years (range: 31-67 years). Four patients were female, including one who was pregnant at the time of infection. All five were hospitalized. One death and one miscarriage were reported.

Live attenuated influenza vaccines offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing process and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild type A/Leningrad/134/1957 and cold-adapted (ca) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV) we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) viruses. A mouse model of infection was used to determine the infectivity and tissue tropism of the parent wt viruses as compared to the ca master donor viruses as well as the H5N1 resassortants. All ca viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the ca MDV. Mice inoculated twice four weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous wt H5N1 HPAI. The profiles of viral replication in respiratory tissues, immunogenicity and protective efficacy characteristics of the two ca H5N1 candidate LAIV warrant further development into a vaccine for human use.

In August 2012, the Arkansas Department of Health (ADH) was notified of gastrointestinal illness outbreaks in two Arkansas state prisons. ADH investigated the outbreaks and conducted case-control studies to identify the source of the illnesses. This report describes the results of these investigations, which identified 528 persons with onset of diarrhea during August 2-18, 2012. Results from the prison A investigation identified chicken salad as the most likely vehicle. At prison B, person-to-person transmission and contamination of multiple foods likely contributed to illness. Analysis of stool specimens from inmates identified eight serotypes and 15 pulsed-field gel electrophoresis (PFGE) patterns of Salmonella. Isolates of Salmonella from eggs produced at prison B matched two outbreak patterns. An additional 69 inmates were positive by culture but were not interviewed or did not report diarrhea, making the total case count 597. Sanitarians identified problems with food preparation, hand washing, and food safety training. ADH tested inmate kitchen workers, excluded infected inmates from work, and provided food safety training. Prison kitchen staff should follow guidelines consistent with state regulations for safe food preparation and pass sanitarian inspection.

BACKGROUND: Combination antiretroviral therapy (ART) has significantly increased survival among HIV-positive adults in the United States (U.S.) and Canada, but gains in life expectancy for this region have not been well characterized. We aim to estimate temporal changes in life expectancy among HIV-positive adults on ART from 2000-2007 in the U.S. and Canada. METHODS: Participants were from the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), aged ≥20 years and on ART. Mortality rates were calculated using participants' person-time from January 1, 2000 or ART initiation until death, loss to follow-up, or administrative censoring December 31, 2007. Life expectancy at age 20, defined as the average number of additional years that a person of a specific age will live, provided the current age-specific mortality rates remain constant, was estimated using abridged life tables. RESULTS: The crude mortality rate was 19.8/1,000 person-years, among 22,937 individuals contributing 82,022 person-years and 1,622 deaths. Life expectancy increased from 36.1 [standard error (SE) 0.5] to 51.4 [SE 0.5] years from 2000-2002 to 2006-2007. Men and women had comparable life expectancies in all periods except the last (2006-2007). Life expectancy was lower for individuals with a history of injection drug use, non-whites, and in patients with baseline CD4 counts <350 cells/mm(3). CONCLUSIONS: A 20-year-old HIV-positive adult on ART in the U.S. or Canada is expected to live into their early 70 s, a life expectancy approaching that of the general population. Differences by sex, race, HIV transmission risk group, and CD4 count remain.

In an effort to detect West Nile virus (WNV) in Brazil, we sampled serum from horses and chickens from the Pantanal region of the state of Mato Grosso and tested for flavivirus-reactive antibodies by blocking ELISA. The positive samples were further confirmed for serological evidence of WNV infection in three (8%) of the 38 horses and one (3.2%) of the 31 chickens using an 80% plaque-reduction neutralisation test (PRNT 80). These results provide evidence of the circulation of WNV in chickens and horses in Pantanal.

In 2007, a National Park Service (NPS) biologist died from pneumonic plague after unprotected exposure to an infected mountain lion. This incident increased awareness of occupational zoonotic disease transmission and prompted an assessment of employees who handle wildlife. During April-June 2009, we conducted a national online survey of NPS biologists and other wildlife workers to assess in the preceding 12 mo: 1) potential work-related zoonotic disease exposures; 2) protective practices, including use of personal protective equipment (PPE); and 3) barriers and facilitators to PPE use. Summary protective measure scores were calculated and compared with sociodemographic and work-related factors. Surveys were completed by 238 employees from 131 parks in all NPS regions. Seventy-one percent were biologists or technicians, 16% natural resource specialists or managers, and 13% had other job titles. Among a majority of respondents, interactions with animals were infrequent and occurred approximately several times per year as follows: handling live (39%), sick (43%), or dead animals (46%), and drawing blood from animals (42%). The most frequently reported protective measures used were hand hygiene and gloves. Commonly agreed-upon measures that would facilitate PPE use included having PPE stocked and readily available (92%) and having specific PPE kits for use during necropsies (91%) and in remote field settings (91%). Significantly higher summary protective measure scores were found if respondents had either read or reviewed "NPS safe work practices for employees handling wildlife" with their supervisor, had zoonotic disease safety or PPE use included in their employee performance appraisal plans, or had conducted a job-hazard analysis for handling wildlife. Ninety (38%) respondents reported receiving zoonotic disease training. Our findings support the development and implementation of workplace interventions to increase zoonotic disease awareness and promote a culture of prevention among wildlife professionals.

BACKGROUND: By supplementing an index composed of HIV biomarkers and age (restricted index) with measures of organ injury, the Veterans Aging Cohort Study (VACS) index more completely reflects risk of mortality. We compare the accuracy of the VACS and restricted indices (1) among subjects outside the Veterans Affairs Healthcare System, (2) more than 1-5 years of prior exposure to antiretroviral therapy (ART), and (3) within important patient subgroups. METHODS: We used data from 13 cohorts in the North American AIDS Cohort Collaboration (n = 10, 835) limiting analyses to HIV-infected subjects with at least 12 months exposure to ART. Variables included demographic, laboratory (CD4 count, HIV-1 RNA, hemoglobin, platelets, aspartate and alanine transaminase, creatinine, and hepatitis C status), and survival. We used C-statistics and net reclassification improvement (NRI) to test discrimination varying prior ART exposure from 1 to 5 years. We then combined Veterans Affairs Healthcare System (n = 5066) and North American AIDS Cohort Collaboration data, fit a parametric survival model, and compared predicted to observed mortality by cohort, gender, age, race, and HIV-1 RNA level. RESULTS: Mean follow-up was 3.3 years (655 deaths). Compared with the restricted index, the VACS index showed greater discrimination (C-statistics: 0.77 vs. 0.74; NRI: 12%; P < 0.0001). NRI was highest among those with HIV-1 RNA <500 copies per milliliter (25%) and age ≥50 years (20%). Predictions were similar to observed mortality among all subgroups. CONCLUSIONS: VACS index scores discriminate risk and translate into accurate mortality estimates over 1-5 years of exposure to ART and for diverse patient subgroups from North American.

OBJECTIVE: HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection - the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women. METHODS: Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction. RESULTS: A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥350, 200-349 and <200 cells/uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (P(trend) =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results. CONCLUSIONS: This study found elevated incidence of ICC in HIV-infected compared to -uninfected women, and these rates increased with immunosuppression.