INTRODUCTION: Fall injuries are the second leading cause of traumatic injury and death for all US workers and are a leading injury concern for the Department of the Air Force (DAF). Bundled interventions can improve the likelihood of injury reduction, especially in large, heterogeneous working populations. In 2013, the DAF implemented the "Air Force Fall Prevention Focus," a bundled intervention of prevention efforts designed to reduce occupational fall injury events among DAF members. The purpose of this study is to describe the burden and risk factors associated with fall injuries and evaluate the effectiveness of the Fall Prevention Focus in reducing the burden of fall injuries. METHODS: The National Institute for Occupational Safety and Health (NIOSH) partnered with the US Air Force Safety Center (AFSEC) to examine the impact of the Fall Prevention Focus as a bundled intervention. Injury events included a narrative description of the injury event, demographics, work environment, job tasks, and other structured details. Descriptive statistics and pre-post longitudinal modeling were used to evaluate changes in fall injury rates. RESULTS: The Fall Prevention Focus Implementation (2013-2018) resulted in an annual 10.4% (95% confidence interval [CI]: 8.5%, 12.2%) reduction, and a 6-year cumulative 48.3% (95% CI: 41.4%, 54.3%) reduction in fall injury event rates by 2018. DISCUSSION: Safety in the DAF involves a comprehensive approach. Documenting the impact of the Fall Prevention Focus may help translate these findings to improve fall prevention efforts in other sectors of the military and high fall-risk industries in the private sector, such as construction.

BACKGROUND: Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years. METHODS: We undertook a systematic review (Jan 1, 2000-July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5-7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2-3 or days 5-7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085. FINDINGS: In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0-55·9) following treatment without primaquine, 16·0% (12·4-20·3) following a low total dose of primaquine, and 10·2% (8·4-12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11-0·25) and high total doses (0·09, 0·07-0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18-0·59) for a low total dose and 0·13 (0·08-0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35-0·85) and children younger than 5 years (0·41, 0·21-0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5-7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0-8·6) in children not treated with primaquine, 9·2% (0-18·7) with a low daily dose of primaquine, 6·8% (1·7-12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8-14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1-1·5), a low daily dose (0·0%, 0·0-1·6), an intermediate daily dose (0·5%, 0·1-1·4), or a high daily dose (0·7%, 0·2-1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine. INTERPRETATION: A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events. FUNDING: Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council.

Workplace and non-workplace homicides in the United States (U.S.) have declined for over 30 years until recently. This study was conducted to address the change in trends for both workplace and non-workplace homicides and to evaluate the homogeneity of the change in workplace homicides by specified categories. Joinpoint and autoregressive models were used to assess trends of U.S. workplace and non-workplace homicides utilizing surveillance data collected by the Bureau of Labor Statistics and the Federal Bureau of Investigation from 1994 through 2021. Both workplace and non-workplace homicides decreased significantly from 1994 through 2014. Workplace homicides showed no significant trend from 2014 through 2021 (p = 0.79), while non-workplace homicides showed a significant average annual increase of 4.1% from 2014 through 2020 (p = 0.0013). The large decreases in the trend of workplace homicides occurring during a criminal act, such as robbery, leveled off and started to increase by the end of the study period (p < 0.0001). Declines in workplace homicides due to shootings also leveled off and started to increase by the end of the study period (p < 0.0001). U.S. workplace and non-workplace homicide rates declined from the 1990s until around 2014. Trends in workplace homicides varied by the types of the homicide committed and by the type of employee that was the victim. Criminal-intent-related events, such as robbery, appear to be the largest contributor to changes in workplace homicides. Researchers and industry leaders could develop and evaluate interventions that further address criminal-intent-related workplace homicides.

COVID-19 has been associated with an increased risk for thromboembolic events, including ischemic stroke, venous thromboembolism, and myocardial infarction. Studies have reported lower rates of COVID-19-related thromboembolic events among persons who received the COVID-19 vaccine compared with persons who did not, but rigorous estimates of vaccine effectiveness (VE) in preventing COVID-19-related thromboembolic events are lacking. This analysis estimated the incremental benefit of receipt of a bivalent mRNA COVID-19 vaccine after receiving an original monovalent COVID-19 vaccine. To estimate VE of a bivalent mRNA COVID-19 dose in preventing thromboembolic events compared with original monovalent COVID-19 vaccine doses only, two retrospective cohort studies were conducted among Medicare fee-for-service enrollees during September 4, 2022-March 4, 2023. Effectiveness of a bivalent COVID-19 vaccine dose against COVID-19-related thromboembolic events compared with that of original vaccine alone was 47% (95% CI = 45%-49%) among Medicare enrollees aged ≥65 years and 51% (95% CI = 39%-60%) among adults aged ≥18 years with end stage renal disease receiving dialysis. VE was similar among Medicare beneficiaries with immunocompromise: 46% (95% CI = 42%-49%) among adults aged ≥65 years and 45% (95% CI = 24%-60%) among those aged ≥18 years with end stage renal disease. To help prevent complications of COVID-19, including thromboembolic events, adults should stay up to date with COVID-19 vaccination.

Problem: Employers are required to report severe work-related injuries (e.g., amputation, inpatient hospitalization, or loss of an eye), to the Occupational Safety and Health Administration (OSHA). This study examined the OSHA severe injury reports (SIRs) public microdata to understand time-related trends and patterns. Methods: This study included all SIRs from January 2015 to December 2021 (84&#160;months). We employed time series decomposition models (classical additive and multiplicative, X-11, and X-13ARIMA-SEATS) to evaluate monthly seasonal effect and seasonally adjusted trend of SIRs. We developed data visuals to display trends from different models with the original data series. We compared number of daily SIRs by day of the week, and yearly trends by 2-digit NAICS and separately by 1-digit OIICS injury event. Results: There were a total of 70,241 SIRs in this 7&#160;year period; ranging from 8,704 to 11,156 per year, and 600 to 1,100 per month. Seasonally adjusted trend indicated a gradual increase of SIRs over time until October 2018, then a steeper decrease until August 2020, and staying somewhat flat for the rest of the months. Seasonality indicated more SIRs were reported in the summer months (June, July, August). Daily SIRs indicated a weekday average of 34 (SD&#160;=&#160;9) and weekend average of 11 (SD&#160;=&#160;5). The Manufacturing and Construction industries reported the highest yearly SIRs. Contact with objects and equipment, and falls, slips, trips were the most numerous injury events associated with SIRs. Discussion: Although Federal OSHA SIR data do not include SIRs from state-plan jurisdictions, the data provide a timely national trend of SIR. This is the first known time series analysis of SIRs. Practical Applications: The findings of this study highlight the ability of researchers to use the SIRs as a timely indicator to understand occupational injury trends by specific industries and injury events.

Problem: Employers are required to report severe work-related injuries (e.g., amputation, inpatient hospitalization, or loss of an eye), to the Occupational Safety and Health Administration (OSHA). This study examined the OSHA severe injury reports (SIRs) public microdata to understand time-related trends and patterns. Methods: This study included all SIRs from January 2015 to December 2021 (84&#160;months). We employed time series decomposition models (classical additive and multiplicative, X-11, and X-13ARIMA-SEATS) to evaluate monthly seasonal effect and seasonally adjusted trend of SIRs. We developed data visuals to display trends from different models with the original data series. We compared number of daily SIRs by day of the week, and yearly trends by 2-digit NAICS and separately by 1-digit OIICS injury event. Results: There were a total of 70,241 SIRs in this 7&#160;year period; ranging from 8,704 to 11,156 per year, and 600 to 1,100 per month. Seasonally adjusted trend indicated a gradual increase of SIRs over time until October 2018, then a steeper decrease until August 2020, and staying somewhat flat for the rest of the months. Seasonality indicated more SIRs were reported in the summer months (June, July, August). Daily SIRs indicated a weekday average of 34 (SD&#160;=&#160;9) and weekend average of 11 (SD&#160;=&#160;5). The Manufacturing and Construction industries reported the highest yearly SIRs. Contact with objects and equipment, and falls, slips, trips were the most numerous injury events associated with SIRs. Discussion: Although Federal OSHA SIR data do not include SIRs from state-plan jurisdictions, the data provide a timely national trend of SIR. This is the first known time series analysis of SIRs. Practical Applications: The findings of this study highlight the ability of researchers to use the SIRs as a timely indicator to understand occupational injury trends by specific industries and injury events.

OBJECTIVE: Fingers, hands, and wrists (FHW) are the most frequently injured body parts in work-related injuries. This study described and compared FHW injuries among enlisted, officer, and civilian U.S. Air Force (USAF) personnel to those in the U.S. workforce. METHODS: All work-related, non-combat FHW injuries (>1 lost workday) and demographics among USAF personnel and U.S. workforce (2008-2018) were included. USAF FHW injury rates were age-adjusted to the U.S. employment and compared by gender, source, event, and nature of the injuries. RESULTS: FHW injuries were significantly lower among the USAF personnel and among females. In both populations FHW injuries from falls were higher and increased with age group among females. Males had higher overall FHW injuries from contact with objects and equipment. CONCLUSIONS: Prevention efforts should focus on understanding risk factors and sharing successful prevention activities.

The coronavirus disease pandemic has highlighted the need to establish and maintain strong infection prevention and control (IPC) practices, not only to prevent healthcare-associated transmission of SARS-CoV-2 to healthcare workers and patients but also to prevent disruptions of essential healthcare services. In East Africa, where basic IPC capacity in healthcare facilities is limited, the US Centers for Disease Control and Prevention (CDC) supported rapid IPC capacity building in healthcare facilities in 4 target countries: Tanzania, Ethiopia, Kenya, and Uganda. CDC supported IPC capacity-building initiatives at the healthcare facility and national levels according to each country's specific needs, priorities, available resources, and existing IPC capacity and systems. In addition, CDC established a multicountry learning network to strengthen hospital level IPC, with an emphasis on peer-to-peer learning. We present an overview of the key strategies used to strengthen IPC in these countries and lessons learned from implementation.

BACKGROUND: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. METHODS: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. FINDINGS: We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34 178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5·7%) of 736 ABT-exposed pregnancies compared with 96 (8·9%) of 1074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0·71, 95% CI 0·49-1·03). Similar results were seen for the individual components of miscarriage (aHR=0·74, 0·47-1·17), stillbirth (aHR=0·71, 0·32-1·57), and major congenital anomalies (aHR=0·60, 0·13-2·87). The risk of adverse pregnancy outcomes was lower with artemether-lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4·8%] of 524 vs 84 [9·2%] of 915; aHR 0·58, 0·36-0·92). INTERPRETATION: We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy. Given that treatment with artemether-lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of ACTs, artemether-lumefantrine should be considered the preferred treatment for uncomplicated P falciparum malaria in the first trimester. If artemether-lumefantrine is unavailable, other ACTs (except artesunate-sulfadoxine-pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted. FUNDING: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.

Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch(®) and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine.

We describe a fatal case of multisystem inflammatory syndrome in an adult with onset 22 days after a second dose of mRNA coronavirus disease vaccine. Serologic and clinical findings indicated severe acute respiratory syndrome coronavirus 2 infection occurred before vaccination. The immunopathology of this syndrome, regardless of vaccination status, remains poorly understood.

According to the WHO, the Region of the Americas has the second lowest tobacco use prevalence of any WHO region.1 WHO projections based on trends since 2000 indicate that the Region of the Americas, which includes both North and South America, is the only region expected to achieve a 30% relative reduction in tobacco use by 2025.1 However, there are approximately 127 million persons who report smoking tobacco in the Americas Region,2 a majority of whom reside in North America.3 North America consists of 23 countries (see table 1) with a combined population of nearly 600 million people, or approximately 7.5% of the world’s population in 2019.4 Among North American countries, data from 2017 for persons aged 15 years or older show current tobacco smoking prevalence ranged from 6.0% in Panama to 27.8% in Cuba.5 Among students aged 13–15 years old in North American countries with available data through 2017, current tobacco smoking prevalence ranged from 4.4% in Dominican Republic to 18.1% in Mexico.5 Tobacco smoking among adults is higher among males than females across North America. However, the difference in prevalence between sexes in the Region of the Americas is among the lowest of any WHO region5; this pattern is particularly pronounced among youth, where tobacco smoking among girls is similar to or higher among boys in most countries.2 5

Introduction: accurate and timely laboratory diagnosis of yellow fever (YF) is critical to the Eliminate Yellow Fever Epidemics (EYE) strategy. Gavi, the Vaccine Alliance recognized the need to support and build capacity in the national and regional laboratories in the Global YF Laboratory Network (GYFLN) as part of this strategy. Method(s): to better understand current capacity, gaps and needs of the GYFLN laboratories in Africa, assessments were carried out in national and regional reference laboratories in the 25 African countries at high risk for YF outbreaks that were eligible for new financial support from Gavi. Result(s): the assessments found that the GYFLN in Africa has high capacity but 21% of specimens were not tested due to lack of testing kits or reagents and approximately 50% of presumptive YF cases were not confirmed at the regional reference laboratory due to problems with shipping. Conclusion(s): the laboratory assessments helped to document the baseline capacities of these laboratories prior to Gavi funding to support strengthening YF laboratories. Copyright © Barbara Wilmot Johnson et al.

PURPOSE: To conduct a systematic review of the effectiveness of interventions to prevent occupational hearing loss, following up on the findings of the most recent version of Cochrane systematic review on the same topic. RESEARCH STRATEGY: Searches were carried out in PubMed, Web of Science and Scopus databases. SELECTION CRITERIA: The following interventions were considered: engineering/administrative controls; hearing protection devices (HPD); and audiological monitoring. DATA ANALYSIS: For bias risk analysis, each study was assessed according to randomization, allocation, blinding, outcomes, other sources of bias. RESULTS: 475 references were obtained. Of these, 17 studies met the inclusion criteria: one randomized, one interrupted time series, and 15 before and after studies. Most studies were conducted in industries; three in military and/or shooting training environments; one in an orchestra, and one in construction. Most studies showed a high risk of bias. Six studies found a reduction in short-term exposure to noise through engineering/administrative controls; one found a positive impact due to changes in legislation; five studies have found positive effects of HPD in reducing exposure to noise and of educational trainings in the use of HPD; lastly, two studies found a reduction in noise levels and an increase in the using of HPD due to the implementation of hearing conservation programs. CONCLUSÃO: Todos os estudos analisados concluíram que as intervenções utilizadas resultaram em efeitos positivos sobre a audição e/ou sobre a exposição ao ruído. Em relação aos efeitos de longo termo, a grande maioria dos estudos limitou-se a avaliar efeitos imediatos ou de curto termo, reforçando que estudos incluindo follow-up de longo termo devem ser desenvolvidos.

We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient's age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes.

We describe transmission of Klebsiella pneumoniae carbapenemase-producing Escherichia coli sequence type (ST) 1193 in a group home. E. coli ST1193 is an emerging multidrug-resistant clone not previously shown to carry carbapenemases in the United States. Our investigation illustrates the potential of residential group homes to amplify rare combinations of pathogens and resistance mechanisms.

BACKGROUND: Targeted testing and treatment (TTT) for latent tuberculosis infection (LTBI) is a recommended strategy to accelerate TB reductions and further tuberculosis elimination in the United States (US). Evidence on cost-effectiveness of TTT for key populations can help advance this goal. METHODS: We used a model of TB transmission to estimate the numbers of individuals who could be tested by interferon-gamma release assay (IGRA) and treated for LTBI with three months of self-administered rifapentine and isoniazid (3HP) under various TTT scenarios. Specifically, we considered rapidly scaling up TTT among people who are non-US-born, diabetic, HIV-positive, homeless or incarcerated in California, Florida, New York, and Texas - states where more than half of US TB cases occur. We projected costs (from the healthcare system perspective, in 2018 dollars), thirty-year reductions in TB incidence, and incremental cost effectiveness (cost per quality-adjusted life year [QALY] gained) for TTT in each modeled population. RESULTS: The projected cost effectiveness of TTT differed substantially by state and population, while the health impact (number of TB cases averted) was consistently greatest among the non-US-born. TTT was most cost-effective among persons living with HIV (from $2,828/QALY gained in Florida to $11,265/QALY gained in New York) and least cost-effective among people with diabetes (from $223,041/QALY gained in California to $817,753 /QALY in New York). CONCLUSIONS: The modeled cost-effectiveness of TTT for LTBI varies across states but was consistently greatest among people living with HIV, moderate among people who are non-US-born, incarcerated, or homeless, and least cost-effective among people living with diabetes.

The first reported U.S. case of coronavirus disease 2019 (COVID-19) was detected in January 2020 (1). As of June 15, 2020, approximately 2 million cases and 115,000 COVID-19-associated deaths have been reported in the United States.* Reports of U.S. patients hospitalized with SARS-CoV-2 infection (the virus that causes COVID-19) describe high proportions of older, male, and black persons (2-4). Similarly, when comparing hospitalized patients with catchment area populations or nonhospitalized COVID-19 patients, high proportions have underlying conditions, including diabetes mellitus, hypertension, obesity, cardiovascular disease, chronic kidney disease, or chronic respiratory disease (3,4). For this report, data were abstracted from the medical records of 220 hospitalized and 311 nonhospitalized patients aged >/=18 years with laboratory-confirmed COVID-19 from six acute care hospitals and associated outpatient clinics in metropolitan Atlanta, Georgia. Multivariable analyses were performed to identify patient characteristics associated with hospitalization. The following characteristics were independently associated with hospitalization: age >/=65 years (adjusted odds ratio [aOR] = 3.4), black race (aOR = 3.2), having diabetes mellitus (aOR = 3.1), lack of insurance (aOR = 2.8), male sex (aOR = 2.4), smoking (aOR = 2.3), and obesity (aOR = 1.9). Infection with SARS-CoV-2 can lead to severe outcomes, including death, and measures to protect persons from infection, such as staying at home, social distancing (5), and awareness and management of underlying conditions should be emphasized for those at highest risk for hospitalization with COVID-19. Measures that prevent the spread of infection to others, such as wearing cloth face coverings (6), should be used whenever possible to protect groups at high risk. Potential barriers to the ability to adhere to these measures need to be addressed.

Noroviruses are a leading cause of endemic and epidemic acute gastroenteritis in all age groups. However, in Latin America there are limited and updated data regarding circulating genotypes. The aim of this study was to assess the prevalence and genetic diversity of norovirus outbreaks in Argentina from 2013-2018. Stool samples from 29 AGE outbreaks were available for viral testing. Norovirus was detected in samples from 18 (62.1%) outbreaks (2 GI and 16 GII). Both GI outbreaks were typed as GI.6[P11] whereas 10 different GII genotypes were detected, in which GII.4 viruses were the most frequently detected (29.4%, associated with GII.P31 and GII.P16) followed by GII.1[P33] and GII.6[P7] (17.6% each). Like GII.4 viruses, GII.2 viruses were also detected in association with different polymerases (GII.P2 and GII.P16). Our findings underscore the importance of dual RdRp-VP1 typing since recombinant strains with new polymerase sequences emerge frequently suggesting a possible role in improved fitness of these viruses. This study represents the most recent multi-year assessment of the molecular epidemiology of norovirus strains associated with AGE outbreaks in Argentina. Molecular surveillance of norovirus has to be considered to monitor possible changes in dominant genotypes which may assist to inform the formulation of future vaccines. This article is protected by copyright. All rights reserved.

BACKGROUND: In July 2018, the Arkansas Department of Health (ADH) was notified by Hospital A of three patients with bloodstream infections (BSIs) with a rapidly growing, nontuberculous Mycobacterium (NTM) species; on September 5, 2018, six additional BSIs were reported. All were among oncology patients at Clinic A. We investigated to identify sources and to prevent further infections. METHODS: ADH performed an onsite investigation at Clinic A on September 7, 2018 and reviewed patient charts, obtained environmental samples, and cultured isolates. Isolates were sequenced (whole genome, 16S, rpoB) by the Centers for Disease Control and Prevention to determine species identity and relatedness. RESULTS: By December 31, 2018, 52 (34%) of 151 oncology patients with chemotherapy ports accessed at Clinic A during March 22-September 12, 2018 had NTM BSIs. Infected patients received significantly more saline flushes than uninfected patients (P <0.001) during the risk period. NTM grew from 6 unused saline flushes compounded by Clinic A. The identified species was novel and designated Mycobacterium FVL 201832. Isolates from patients and saline flushes were highly related by whole-genome sequencing, indicating a common source. Clinic A changed to prefilled saline flushes on September 12 as recommended. CONCLUSIONS: Mycobacterium FVL 201832 caused BSIs in oncology clinic patients. Laboratory data allowed investigators to rapidly link infections to contaminated saline flushes; cooperation between multiple institutions resulted in timely outbreak resolution. New state policies being considered because of this outbreak include adding extrapulmonary NTM to ADH's reportable disease list and providing more oversight to outpatient oncology clinics.

Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT90). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.

Background: Klebsiella pneumoniae carbapenemase-producing organisms (KPCOs) are often multidrug-resistant, and the KPC resistance determinant can be transmitted between bacteria. KPCOs are associated with healthcare facility exposures; identification in community-based, residential care settings is uncommon. In September 2018, the Washoe County Health District was notified of a KPC-producing Escherichia coli from a group home (GH) resident. We investigated the source of this KPCO and evaluated transmission in the GH. Methods: A case was defined as detection of KPCO from a GH resident or staff from June 1 to November 30, 2018. Staff included caregivers who provided daily care (including toileting, bathing, feeding) and visiting healthcare workers. Residents and staff were offered KPCO screening to assess colonization status. Exposures were assessed by medical record review and interviews. Genetic relatedness of KPCOs was evaluated by whole-genome sequencing (WGS). Infection prevention and control (IPC) practices were reviewed. Results: Overall, six cases were identified, including the index, two of seven staff screened and three of six residents screened. Three residents with KPCOs had recent hospitalizations and shared a bathroom in the GH; one overlapped on the same hospital unit as a patient with KPC-producing Klebsiella oxytoca. Staff with KPCOs were caregivers who had extensive contact with residents and their environment and no IPC training. Gaps in hand hygiene and environmental cleaning were observed. Organism was recovered from 4 positive screening tests as well as from blood cultures from the index case; all were KPC-producing E. coli. WGS showed that the five E. coli isolates were closely related, consistent with transmission, and harbored the same KPC variant as the K. oxytoca. No new cases occurred after IPC was improved. Conclusion: A GH resident likely acquired KPCOs during a recent hospitalization, and extensive transmission among GH residents and staff occurred. Factors contributing to transmission included resident dependence on caregivers for daily care and minimal IPC knowledge among caregivers. Facilities with similar populations should increase IPC training to prevent transmission of resistant pathogens. Disclosures: All authors: No reported disclosures.

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.

BACKGROUND: Malaria causes a reduction in haemoglobin that is compounded by primaquine, particularly in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The aim of this study was to determine the relative contributions to red cell loss of malaria and primaquine in patients with uncomplicated Plasmodium vivax. METHODS: A systematic review identified P. vivax efficacy studies of chloroquine with or without primaquine published between January 2000 and March 2017. Individual patient data were pooled using standardised methodology, and the haematological response versus time was quantified using a multivariable linear mixed effects model with non-linear terms for time. Mean differences in haemoglobin between treatment groups at day of nadir and day 42 were estimated from this model. RESULTS: In total, 3421 patients from 29 studies were included: 1692 (49.5%) with normal G6PD status, 1701 (49.7%) with unknown status and 28 (0.8%) deficient or borderline individuals. Of 1975 patients treated with chloroquine alone, the mean haemoglobin fell from 12.22 g/dL [95% CI 11.93, 12.50] on day 0 to a nadir of 11.64 g/dL [11.36, 11.93] on day 2, before rising to 12.88 g/dL [12.60, 13.17] on day 42. In comparison to chloroquine alone, the mean haemoglobin in 1446 patients treated with chloroquine plus primaquine was - 0.13 g/dL [- 0.27, 0.01] lower at day of nadir (p = 0.072), but 0.49 g/dL [0.28, 0.69] higher by day 42 (p < 0.001). On day 42, patients with recurrent parasitaemia had a mean haemoglobin concentration - 0.72 g/dL [- 0.90, - 0.54] lower than patients without recurrence (p < 0.001). Seven days after starting primaquine, G6PD normal patients had a 0.3% (1/389) risk of clinically significant haemolysis (fall in haemoglobin > 25% to < 7 g/dL) and a 1% (4/389) risk of a fall in haemoglobin > 5 g/dL. CONCLUSIONS: Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia. Its widespread implementation will require accurate diagnosis of G6PD deficiency to reduce the risk of drug-induced haemolysis in vulnerable individuals. TRIAL REGISTRATION: This trial was registered with PROSPERO: CRD42016053312. The date of the first registration was 23 December 2016.

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of 5 mg folic acid (FA) daily and serum concentrations of folate, unmetabolized folic acid (UMFA), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha); and mRNA expression of dihydrofolate reductase (DHFR), methylene tetrahydrofolate reductase (MTHFR), IL8, IFNG and TNFA genes. Total serum folate and folate forms were measured in 27 patients with HS (21 users [HS-U] and 6 non-users [HS-NU] of supplemental FA) and 54 healthy controls not consuming 5 mg/day supplemental FA. Each patient was matched to two controls based on age, sex and body mass index. The mononuclear leucocyte mRNA expression of relevant genes and their products were determined. Serum folate, UMFA, 5-methyl-tetrahydrofolate (5-methyl-THF) and tetrahydrofolate (THF) concentrations were significantly higher in HS-U compared with matched healthy controls (p<0.001, n=42). HS-NU had lower serum folate concentrations than matched healthy controls (p=0.044, n=12). HS-U and HS-NU presented similar hematological and biochemical markers profiles. No differences were found between HS-U and HS-NU for cytokine serum concentrations and mRNA expression genes. DHFR mRNA expression was higher in HS-U than in HS-NU. The use of high daily doses of FA for treatment of patients with HS may be excessive and is associated with elevated serum UMFA and elevated DHFR mRNA expression. It is not known whether long-term high-dose FA use by patients with HS might have adverse health effects.

Borrelia burgdorferi was discovered to be the cause of Lyme disease in 1983, leading to seroassays. The 1994 serodiagnostic testing guidelines predated a full understanding of key B. burgdorferi antigens and have a number of shortcomings. These serologic tests cannot distinguish active infection, past infection, or reinfection. Reliable direct-detection methods for active B. burgdorferi infection have been lacking in the past but are needed and appear achievable. New approaches have effectively been applied to other emerging infections and show promise in direct detection of B. burgdorferi infections.

BACKGROUND: Chloroquine remains the mainstay of treatment for Plasmodium vivax malaria despite increasing reports of treatment failure. We did a systematic review and meta-analysis to investigate the effect of chloroquine dose and the addition of primaquine on the risk of recurrent vivax malaria across different settings. METHODS: A systematic review done in MEDLINE, Web of Science, Embase, and Cochrane Database of Systematic Reviews identified P vivax clinical trials published between Jan 1, 2000, and March 22, 2017. Principal investigators were invited to share individual patient data, which were pooled using standardised methods. Cox regression analyses with random effects for study site were used to investigate the roles of chloroquine dose and primaquine use on rate of recurrence between day 7 and day 42 (primary outcome). The review protocol is registered in PROSPERO, number CRD42016053310. FINDINGS: Of 134 identified chloroquine studies, 37 studies (from 17 countries) and 5240 patients were included. 2990 patients were treated with chloroquine alone, of whom 1041 (34.8%) received a dose below the target 25 mg/kg. The risk of recurrence was 32.4% (95% CI 29.8-35.1) by day 42. After controlling for confounders, a 5 mg/kg higher chloroquine dose reduced the rate of recurrence overall (adjusted hazard ratio [AHR] 0.82, 95% CI 0.69-0.97; p=0.021) and in children younger than 5 years (0.59, 0.41-0.86; p=0.0058). Adding primaquine reduced the risk of recurrence to 4.9% (95% CI 3.1-7.7) by day 42, which is lower than with chloroquine alone (AHR 0.10, 0.05-0.17; p<0.0001). INTERPRETATION: Chloroquine is commonly under-dosed in the treatment of vivax malaria. Increasing the recommended dose to 30 mg/kg in children younger than 5 years could reduce substantially the risk of early recurrence when primaquine is not given. Radical cure with primaquine was highly effective in preventing early recurrence and may also improve blood schizontocidal efficacy against chloroquine-resistant P vivax. FUNDING: Wellcome Trust, Australian National Health and Medical Research Council, and Bill & Melinda Gates Foundation.

The cause of Lyme disease, Borrelia burgdorferi, was discovered in 1983. A 2-tiered testing protocol was established for serodiagnosis in 1994, involving an enzyme immunoassay (EIA) or indirect fluorescence antibody, followed (if reactive) by immunoglobulin M and immunoglobulin G Western immunoblots. These assays were prepared from whole-cell cultured B. burgdorferi, lacking key in vivo expressed antigens and expressing antigens that can bind non-Borrelia antibodies. Additional drawbacks, particular to the Western immunoblot component, include low sensitivity in early infection, technical complexity, and subjective interpretation when scored by visual examination. Nevertheless, 2-tiered testing with immunoblotting remains the benchmark for evaluation of new methods or approaches. Next-generation serologic assays, prepared with recombinant proteins or synthetic peptides, and alternative testing protocols, can now overcome or circumvent many of these past drawbacks. This article describes next-generation serodiagnostic testing for Lyme disease, focusing on methods that are currently available or near-at-hand.

Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon gamma (IFNG), tumor necrosis factor alpha (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers.Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells.Results: Serum folate concentrations increased by approximately 5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9- and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (>1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both).Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.govbr as RBR-2pr7zp.

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naive individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.