We report the complete genome sequences of nine double recombinant vaccine-derived novel oral poliovirus type 2 genomes from acute flaccid paralysis (AFP) cases (n = 3), AFP case contacts (n = 4), and environmental surveillance sampling (n = 2) in Nigeria.

Measles is a highly contagious disease and remains a major cause of child mortality worldwide. While measles vaccine is highly effective, high levels of population immunity are needed to prevent outbreaks. Simple but accurate tools are needed to estimate the profile of population measles immunity by age to identify and fill immunity gaps caused by low levels of vaccination coverage. The measles immunity profile estimates and visualizes the percentage of each birth cohort immune or susceptible to measles based on measles vaccination coverage. Several tools that employed this approach have been developed in the past, including informal unpublished versions. However, these tools used varying assumptions and produced inconsistent results. We updated the measles population immunity profile methodology to standardize and better document the assumptions and methods; provide timely estimates of measles population immunity; and facilitate prompt actions to close immunity gaps and prevent outbreaks. We recommend assuming that the second dose of the measles-containing vaccine (MCV2) and doses given during supplementary immunization activities (SIAs) first reach children who have been previously vaccinated against measles, so that previously unvaccinated children are reached only when the coverage of MCV2 or SIA is higher than the coverage achieved by all previous measles vaccination opportunities. This updated method provides a conservative estimate of immunization program impact to assess measles outbreak risk and to facilitate early planning of timely preventive SIAs to close population immunity gaps.

Measles or rubella elimination is verified when endemic transmission of the corresponding virus has been absent for over 36 months in a defined area, in the presence of a well-performing surveillance system. This report updates the progress by 47 countries in the WHO African Region towards the goal of attaining verification of measles and rubella elimination in at least 80% of the countries of the region by 2030. We reviewed the WHO-UNICEF vaccination coverage estimates for the first and second doses of measles- and measles-rubella-containing vaccines, as well as the available coverage data for measles supplementary immunization activities, during 2022-2023. We also reviewed the measles-surveillance performance and analyzed the epidemiological trends of measles and rubella as reported in the case-based surveillance database. The WHO-UNICEF estimates of first measles vaccine dose (MCV1) and second measles vaccine dose (MCV2) coverage for the African Region for 2022 were 69% and 45%, respectively. Rubella-containing vaccines have been introduced in the routine immunization program in 32 of 47 (68%) countries as of the end of 2022, with no introductions during 2023. In 2022 and 2023, a total of 144,767,764 children were vaccinated in the region with measles or MR vaccines in 24 countries through 32 mass vaccination campaigns. The administrative coverage target of 95% was reached in only 15 (49%) of the 32 vaccination campaigns. In 2023, a total of 125,957 suspected cases of measles were reported through the case-based surveillance system, and 73,625 cases (58%) were confirmed to be measles, either by laboratory testing, by epidemiological linkage, or based on clinical compatibility. A total of 4805 confirmed rubella cases were reported, though this total represents substantial under-ascertainment. The regional incidence of measles was 60.3 cases per million population. Twenty-six countries (55%) met the targets for the two principal surveillance system performance-monitoring indicators. No country in the region has attained the verification of measles or rubella elimination as of the end of 2023. Addressing systemic problems with routine immunization and using tailored approaches to reach unvaccinated children can contribute to progress towards measles and rubella elimination. In addition, periodic and timely high-quality preventive SIAs remain a critical programmatic strategy to reach unvaccinated children.

There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop.

Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies.

BACKGROUND: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response. OBJECTIVE: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented. To bridge this gap, we proposed sub-national IARs focused on COVID-19 vaccine program implementation at the provincial level. METHODS: Using the WHO methodology, we organized a four-day provincial IAR workshop and invited national, provincial and health zone Ministry of Health (MoH) representatives and private and non-governmental organizations involved in the provincial COVID-19 vaccination response. Participants were divided into six groups based on their expertise, affiliation, and role within the health system to assess and identify lessons learned, challenges and the solutions within each of the six technical areas: (1) coordination, planning and monitoring; (2) service delivery; (3) risk communication and community engagement; (4) adverse effects following immunization (AEFI); (5) logistics; (6) and data management, monitoring and evaluation. RESULTS: The first provincial COVID-19 IAR was conducted in Goma, North Kivu, from January 19-22, 2022. A total of 56 participants came from provincial and health zone offices, and non-governmental organizations. Through work group discussions, they identified best practices, challenges, and lessons learned, and made recommendations to improve implementation of vaccination activities and reach coverage targets. Activities were proposed to operationalize recommendations and address challenges to improve the provincial response. CONCLUSION: This provincial IAR was a useful tool for reviewing progress and areas of improvement, while evaluating aspects of the COVID-19 vaccine rollout. It provided a means to share information with vaccination partners on areas of intervention, tailored to the local context.

BACKGROUND: Adverse childhood experiences (ACEs) have been understudied in low- and middle-income countries, especially in sub-Saharan Africa. OBJECTIVES, PARTICIPANTS, SETTING: We explored associations between mental distress, self-harm or suicidality, and HIV risk and individual and cumulative ACEs (sexual, emotional, and physical violence; witnessing community and interparental violence; orphanhood) among youth aged 13-24 in Lesotho. METHODS: Multivariable logistic regressions stratified by sex using nationally representative 2018 Lesotho Violence Against Children and Youth Survey (n(female) = 7101; n(male) = 1467) data. RESULTS: Over 75 % of males and females experienced at least 1 ACE. Among males, physical and community violence were significantly associated with mental distress; orphan status and emotional violence was associated with self-harm/suicidality. Males who witnessed interparental violence had higher odds of disclosing 2 types and 3 or more types of HIV risk versus none. Among females, being a double orphan and having experienced sexual, emotional, physical, community, and interparental violence were significantly associated with mental distress and any self-harm/suicidality in both models. Females who experienced physical violence had higher odds of disclosing 3 or more risk types versus no risk. Statistically significant associations emerged between cumulative ACEs and mental distress, self-harm/suicidality, and higher levels of HIV risk for both males and females. CONCLUSIONS: Differential patterns of associations between ACEs and mental health problems and HIV risk emerged by sex. Scalable, integrated individual and community efforts to prevent ACEs, provide mental health supports, and encourage safer sexual behaviors among those exposed are needed and could benefit youth in Lesotho.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death in the United States. Certain demographic characteristics are associated with disparities in CVD and its risk factors, which may interact with specific social determinants of health (SDOH). We examined the association of a single SDOH (ie, poverty level) with diagnosed CVD morbidity and the joint influence of poverty and hypertension on the prevalence of CVD morbidity among non-Hispanic Black, non-Hispanic White, and Hispanic people aged 30 years or older. METHODS: We used data from the National Health and Nutrition Examination Survey collected during 1999 to 2018. We assessed the prevalence of diagnosed CVD morbidity (eg, self-reported coronary heart disease, angina, myocardial infarction, or stroke) by using a Poisson family with a log link regression model. We calculated the additive interaction of poverty level with hypertension on diagnosed CVD morbidity for each race and ethnicity. RESULTS: We found excess CVD morbidity among non-Hispanic Black and Hispanic people experiencing poverty and diagnosed with hypertension compared with their non-Hispanic White counterparts. Multivariate analysis found a higher prevalence of CVD among participants of all races and ethnicities who were experiencing poverty and among non-Hispanic White people who had less than a college education. In addition, age, hypertension, poverty, smoking, and weight were significant predictors of the prevalence of CVD morbidity among all racial and ethnic groups. CONCLUSION: Changes to interventions, policies, and research may be needed to address the effect of key indicators of health disparities and specific SDOH, such as poverty level, that intersect with hypertension and contribute to excess CVD morbidity among people of some racial and ethnic groups, particularly non-Hispanic Black and Hispanic populations.

Measles – clinically recognized as fever, rash and one or more of cough, coryza, or conjunctivitis – has been a leading cause of vaccine-preventable disease and death. Despite the existence of a well tolerated and effective vaccine, an estimated 128 000 children worldwide died of measles in 2021 [1]. Measles complications typically include pneumonia and diarrhea, caused either directly by measles virus or indirectly by measles-induced loss of preexisting immunity to common childhood pathogens [2–5]. Among people with HIV (PWH), measles infection can lead to severe pneumonia, encephalitis, and death; among children with HIV (CHIV), the mortality risk doubles [3,6]. | | For infants exposed to HIV in utero or HIV-infected but asymptomatic, WHO recommends a supplementary measles vaccine dose at 6 months of age in addition to the doses routinely recommended by the country's immunization schedule [7]. A measles vaccine dose at 6 months aims to vaccinate these infants soon after they lose maternally derived antibodies and while HIV-infected infants are better able to develop an immune response [8,9]. Although immune reconstitution during antiretroviral therapy (ART) does not restore preexisting measles immunity [10], vaccination after reconstitution can induce protective immunity against measles [11,12]. WHO therefore recommends providing at least one measles vaccine dose after immune reconstitution following ART initiation, or 6–12 months after ART initiation when CD4+ testing is not available [7].

Worldwide, measles remains a major cause of disease and death; the highest incidence is in the World Health Organization African Region (AFR). In 2011, the 46 AFR member states established a goal of regional measles elimination by 2020; this report describes progress during 2017-2021. Regional coverage with a first dose of measles-containing vaccine (MCV) decreased from 70% in 2017 to 68% in 2021, and the number of countries with ≥95% coverage decreased from six (13%) to two (4%). The number of countries providing a second MCV dose increased from 27 (57%) to 38 (81%), and second-dose coverage increased from 25% to 41%. Approximately 341 million persons were vaccinated in supplementary immunization activities, and an estimated 4.5 million deaths were averted by vaccination. However, the number of countries meeting measles surveillance performance indicators declined from 26 (62%) to nine (22%). Measles incidence increased from 69.2 per 1 million population in 2017 to 81.9 in 2021. The number of estimated annual measles cases and deaths increased 22% and 8%, respectively. By December 2021, no country in AFR had received verification of measles elimination. To achieve a renewed regional goal of measles elimination in at least 80% of countries by 2030, intensified efforts are needed to recover and surpass levels of surveillance performance and coverage with 2 MCV doses achieved before the COVID-19 pandemic.

Finding, characterizing, and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive, and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19,933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3,565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement.Originality-Significance Statement This work is applicable to a wide range of research. It helps to define conditions under which hybridization capture is useful regarding not only antimicrobial resistance specifically, but also more generally how to assess the ongoing utility of existing bait sets - giving objective criteria for when and by what strategies baits should be updated. We also provide a method for quantifying and comparing antimicrobial resistance genes (ARGs) similar to what is used for RNAseq experiments. This approach improves comparison of ARGs across environments. Thus, the work provides an improved foundation for ARG future studies, while cutting across traditional areas of microbiology and extending beyond.Competing Interest StatementThe EHS DNA lab provides oligonucleotide aliquots and library preparation services at cost, including some oligonucleotides and services used in this manuscript (baddna.uga.edu). JE and AD were employed by, and thereby have financial interest in, Daicel Arbor Biosciences, who provided the in-solution capture reagents used in this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

HIV and violence among orphans are key measures of vulnerability in low-resource settings. Although Lesotho has the second highest HIV adult prevalence rate (21.1%) in the world, and the prevalence of orphanhood (44.2%) and violence exposure (67.0%) is high, little research exist on orphanhood vulnerabilities for violence and HIV in Lesotho. Using data from 4,408 youth (18-24 years old) from Lesotho's 2018 Violence Against Children and Youth survey, a nationally representative cross-sectional household survey, the study examined associations among orphan status, violence, and HIV and assessed how associations differed by education, sex, and orphan type, using logistic regression. Orphans had higher odds of violence (aOR, 1.21; 95% CI, 1.01-1.46) and HIV (aOR, 1.69; 95% CI, 1.24-2.29). Having primary education or less (aOR, 1.43; 95% CI, 1.02-2.02), male sex (aOR, 1.74; 95% CI, 1.27-2.36), and being a paternal orphan (aOR, 1.43; 95% CI, 1.14-1.80) were significant interaction terms for violence. Orphans who completed primary school or less (aOR, 1.61; 95% CI, 1.09-2.39), female (aOR, 3.08; 95% CI, 2.14-4.42) and double orphans (aOR, 2.54; 95% CI, 1.56-4.13) had higher odds of HIV. These relationships highlight the importance of comprehensive strategies to support education and family strengthening for orphans as core violence and HIV prevention efforts.

Global emergence of the COVID-19 pandemic in 2020 curtailed vaccine-preventable disease (VPD) surveillance activities, but little is known about which surveillance components were most affected. In May 2021, we surveyed 214 STOP (originally Stop Transmission of Polio) Program consultants to determine how VPD surveillance activities were affected by the COVID-19 pandemic throughout 2020, primarily in low- and middle-income countries, where program consultants are deployed. Our report highlights the responses from 154 (96%) of the 160 consultants deployed to the World Health Organization African Region, which comprises 75% (160/214) of all STOP Program consultants deployed globally in early 2021. Most survey respondents observed that VPD surveillance activities were somewhat or severely affected by the COVID-19 pandemic in 2020. Reprioritization of surveillance staff and changes in health-seeking behaviors were factors commonly perceived to decrease VPD surveillance activities. Our findings suggest the need for strategies to restore VPD surveillance to prepandemic levels.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

BACKGROUND: Effective surveillance of microbial communities in the healthcare environment is increasingly important in infection prevention. Metagenomics-based techniques are promising due to their untargeted nature but are currently challenged by several limitations: (1) they are not powerful enough to extract valid signals out of the background noise for low-biomass samples, (2) they do not distinguish between viable and nonviable organisms, and (3) they do not reveal the microbial load quantitatively. An additional practical challenge towards a robust pipeline is the inability to efficiently allocate sequencing resources a priori. Assessment of sequencing depth is generally practiced post hoc, if at all, for most microbiome studies, regardless of the sample type. This practice is inefficient at best, and at worst, poor sequencing depth jeopardizes the interpretation of study results. To address these challenges, we present a workflow for metagenomics-based environmental surveillance that is appropriate for low-biomass samples, distinguishes viability, is quantitative, and estimates sequencing resources. RESULTS: The workflow was developed using a representative microbiome sample, which was created by aggregating 120 surface swabs collected from a medical intensive care unit. Upon evaluating and optimizing techniques as well as developing new modules, we recommend best practices and introduce a well-structured workflow. We recommend adopting liquid-liquid extraction to improve DNA yield and only incorporating whole-cell filtration when the nonbacterial proportion is large. We suggest including propidium monoazide treatment coupled with internal standards and absolute abundance profiling for viability assessment and involving cultivation when demanding comprehensive profiling. We further recommend integrating internal standards for quantification and additionally qPCR when we expect poor taxonomic classification. We also introduce a machine learning-based model to predict required sequencing effort from accessible sample features. The model helps make full use of sequencing resources and achieve desired outcomes. Video Abstract CONCLUSIONS: This workflow will contribute to more accurate and robust environmental surveillance and infection prevention. Lessons gained from this study will also benefit the continuing development of methods in relevant fields.

COVID-19 vaccination in the Democratic Republic of the Congo (DRC) began in April 2021. A month later, most COVID-19 vaccine doses were reallocated to other African countries, due to low vaccine uptake and the realization that the doses would expire before use. Based on data available on 13 August 2022, 2.76% of the DRC population had been fully vaccinated with last dose of primary series of COVID-19 vaccine, placing the country second to last in Africa and in the last five in global COVID-19 vaccination coverage. The DRC's reliance on vaccine donations requires continuous adaptation of the vaccine deployment plan to match incoming COVID-19 vaccines shipments. Challenges in planning vaccine deployments, vaccinating priority populations, coordinating, and implementing the communications plan, disbursing funds, and conducting supervision of vaccination activities have contributed to low COVID-19 vaccine coverage. In addition, the spread of rumors through social media and by various community and religious leaders resulted in high levels of vaccine hesitancy. A strong risk communication and community engagement plan, coupled with innovative efforts to target the highest-risk populations are critical to increase vaccine uptake during the next phase of COVID-19 vaccine introduction.

As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders.

BACKGROUND: Invasive mold diseases (IMDs) cause severe illness, but public health surveillance data are lacking. We describe data collected from a laboratory-based, pilot IMD surveillance system. METHODS: During 2017-2019, the Emerging Infections Program conducted active IMD surveillance at 3 Atlanta-area hospitals. We ascertained potential cases by reviewing histopathology, culture, and Aspergillus galactomannan results and classified patients as having an IMD case (based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [MSG] criteria) or a non-MSG IMD case (based on the treating clinician's diagnosis and use of mold-active antifungal therapy). We described patient features and compared patients with MSG vs non-MSG IMD cases. RESULTS: Among 304 patients with potential IMD, 104 (34.2%) met an IMD case definition (41 MSG, 63 non-MSG). The most common IMD types were invasive aspergillosis (n=66 [63.5%]), mucormycosis (n=8 [7.7%]), and fusariosis (n=4 [3.8%]); the most frequently affected body sites were pulmonary (n=66 [63.5%]), otorhinolaryngologic (n=17 [16.3%]), and cutaneous/deep tissue (n=9 [8.7%]). Forty-five (43.3%) IMD patients received intensive care unit-level care, and 90-day all-cause mortality was 32.7%; these outcomes did not differ significantly between MSG and non-MSG IMD patients. CONCLUSIONS: IMD patients had high mortality rates and a variety of clinical presentations. Comprehensive IMD surveillance is needed to assess emerging trends, and strict application of MSG criteria for surveillance might exclude over one-half of clinically significant IMD cases.

BACKGROUND: Long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are the main malaria vector control measures deployed in Kenya. Widespread pyrethroid resistance among the primary vectors in Western Kenya has necessitated the re-introduction of IRS using an organophosphate insecticide, pirimiphos-methyl (Actellic® 300CS), as a pyrethroid resistance management strategy. Evaluation of the effectiveness of the combined use of non-pyrethroid IRS and LLINs has yielded varied results. We aimed to evaluate the effect of non-pyrethroid IRS and LLINs on malaria indicators in a high malaria transmission area. METHODS: We reviewed records and tallied monthly aggregate of outpatient department (OPD) attendance, suspected malaria cases, those tested for malaria and those testing positive for malaria at two health facilities, one from Nyatike, an intervention sub-county, and one from Suba, a comparison sub-county, both located in Western Kenya, from February 1, 2016, through March 31, 2018. The first round of IRS was conducted in February-March 2017 in Nyatike sub-county and the second round one year later in both Nyatike and Suba sub-counties. The mass distribution of LLINs has been conducted in both locations. We performed descriptive analysis and estimated the effect of the interventions and temporal changes of malaria indicators using Poisson regression for a period before and after the first round of IRS. RESULTS: A higher reduction in the intervention area in total OPD, the proportion of OPD visits due to suspected malaria, testing positivity rate and annual malaria incidences were observed except for the total OPD visits among the under 5 children (59% decrease observed in the comparison area vs 33% decrease in the intervention area, net change -27%, P <0.001). The percentage decline in annual malaria incidence observed in the intervention area was more than twice the observed percentage decline in the comparison area across all the age groups. A marked decline in the monthly testing positivity rate (TPR) was noticed in the intervention area, while no major changes were observed in the comparison area. The monthly TPR reduced from 46% in February 2016 to 11% in February 2018, representing a 76% absolute decrease in TPR among all ages (RR = 0.24, 95% CI 0.12-0.46). In the comparison area, TPR was 16% in both February 2016 and February 2018 (RR = 1.0, 95% CI 0.52-2.09). A month-by-month comparison revealed lower TPR in Year 2 compared to Year 1 in the intervention area for most of the one year after the introduction of the IRS. CONCLUSIONS: Our findings demonstrated a reduced malaria burden among populations protected by both non-pyrethroid IRS and LLINs implying a possible additional benefit afforded by the combined intervention in the malaria-endemic zone.

BACKGROUND: Tuberculosis (TB) elimination within the United States (US) will require scaling up TB preventive services. Many public health departments offer care for latent tuberculosis infection (LTBI), though gaps in the LTBI care cascade are not well quantified. An understanding of these gaps will be required to design targeted public health interventions. METHODS: We conducted a cohort study through the Tuberculosis Epidemiologic Studies Consortium (TBESC) within 15 local health department (LHD) TB clinics across the US. Data was abstracted on individuals receiving LTBI care during 2016-2017 through chart review. Our primary objective was to quantify the LTBI care cascade, beginning with LTBI testing and extending through treatment completion. RESULTS: Among 23,885 participants tested by LHDs, 46% (11,009) were male with a median age of 31 (IQR 20-46). A median of 35% of participants were US-born at each site (IQR 11-78). Overall, 16,689 (70%) received a tuberculin skin test (TST), 6,993 (29%) received a Quantiferon (QFT), and 1,934 (8%) received a T-SPOT.TB; 5% (1,190) had more than one test. Among those tested, 2,877 (12%) had at least one positive test result (3% among US-born, and 23% among non-US-born, p<0.01). Of 2,515 (11%) of the total participants diagnosed with LTBI, 1,073 (42%) initiated therapy, of whom 817 (76%) completed treatment (32% of those with LTBI diagnosis). CONCLUSIONS: Significant gaps were identified along the LTBI care cascade, with less than half of individuals diagnosed with LTBI initiating therapy. Further research is needed to better characterize the factors impeding LTBI diagnosis, treatment initiation, and treatment completion.

We report an outbreak of severe acute respiratory syndrome coronavirus 2 involving 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in Tennessee, USA. Investigation identified naturally occurring tiger-to-tiger transmission; genetic sequence change occurred with viral passage. We provide epidemiologic, environmental, and genomic sequencing data for animal and human infections.

Purpose: Adverse childhood experiences (ACEs) are a global public health concern. Little research exists on the prevalence and health consequences of ACEs in Zambia. The current study examined associations between individual and cumulative ACEs, mental distress, and suicide risk among Zambian youth. Methods: Data from Zambia Violence Against Children and Youth Survey were used (18-24 years old, n=1034). Bivariate and adjusted logistic models were performed with independent variables (i.e., experienced physical violence (PV), sexual violence (SV), and emotional violence (EV); witnessed intimate partner violence (IPV) and community violence (CV); orphan status; cumulative ACE exposure) and dependent variables (i.e., mental distress and suicide risk). Adjusted models controlled for demographic and social characteristics. Results: 76.8% of Zambian youth experienced one or more ACEs, and more than 30% witnessed CV (38.4%) or IPV (30.2%), or experienced PV (35.1%), prior to age 18. 27.5% were orphans, and less than 20% experienced EV (17.3%) or SV (15.4%) in childhood. 42.4% experienced mental distress in the past 30 days, and 12.5% reported lifetime suicidal thoughts or suicide attempts. PV, EV, cumulative ACE exposure, older age, being single, and stronger friendships were significantly related to experiencing mental distress. Cumulative ACEs exposure was associated with significantly higher suicide risk. Conclusions: Preventing ACEs can reduce mental distress and suicide risk among Zambian youth. Youth with cumulative ACE exposure can be prioritized for mental health intervention. More research is warranted to investigate the broad-based prevention of ACEs, especially PV and EV, and protective factors that can promote resilience among youth who have experienced ACEs.

Finding, characterizing and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19 933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement.

BACKGROUND: Healthcare-associated infections (HAIs) are a significant economic burden and cause of avoidable morbidity and mortality within healthcare systems. The contribution of environmental contamination to HAI transmission has been recognized, but the mechanisms by which transmission occurs are still being investigated. The objective of this study was to characterize the microbial communities of disinfected, non-critical healthcare surfaces using next generation sequencing technology. METHODS: Composite environmental surface samples were from high-touch surfaces in rooms of patients isolated for infections with multidrug-resistant organisms during their hospitalization. Information on the disinfectant product used and cleaning type (routine or terminal) was collected. 16S rRNA gene amplicon sequencing and analysis were performed. Community analysis was conducted to determine the bacterial composition and compare the detection of target pathogens by culture from 94 Contact Precaution rooms. RESULTS: Overall percent agreement between culture and sequence methods ranged from 52% to 88%. A significant difference was observed in bacterial composition between rooms cleaned with bleach and those cleaned with a quaternary ammonium compound (QAC) for composite 2 (overbed table, intravenous pole, and inner room door handle) (ANOSIM R2 = 0.66, p = 0.005) but not composite 1 (bed rails, television remote control unit, call buttons, and telephone). CONCLUSIONS: Surfaces in bleach-cleaned rooms contained a higher proportion of gram-positive microbiota, whereas rooms cleaned with QAC contained a higher proportion of gram-negative microbiota, suggesting disinfectant products may impact the healthcare environment microbiome.

BACKGROUND: To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents. METHODS: We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts. Blood for serology was collected on days 0, 6, 12, 21, and 42. Infectivity was defined by positive culture. Duration of culture positivity was compared with duration of COVID-19 symptoms and RT-PCR positivity. Data were summarized using measures of central tendency, frequencies, and proportions. RESULTS: We enrolled 17 of 39 (44%) eligible residents. Median participant age was 82 years (range, 58-97 years). All had ≥3 underlying conditions. Median duration of RT-PCR positivity was 22 days (interquartile range [IQR], 8-31 days) from diagnosis; median duration of symptoms was 42 days (IQR, 28-49 days). Of 9 (53%) participants with any culture-positive specimens, 1 (11%) severely immunocompromised participant remained culture-positive 19 days from diagnosis; 8 of 9 (89%) were culture-positive ≤8 days from diagnosis. Seroconversion occurred in 12 of 12 (100%) surviving participants with ≥1 blood specimen; all participants were culture-negative before seroconversion. CONCLUSIONS: Duration of infectivity was considerably shorter than duration of symptoms and RT-PCR positivity. Severe immunocompromise may prolong SARS-CoV-2 infectivity. Seroconversion indicated noninfectivity in this cohort.

Ground control is the science of studying and controlling the behavior of rock strata in response to mining operations. Ground-control-related research has seen significant advancements over the last 40 years, and these accomplishments are well documented in the proceedings of the annual International Conference on Ground Control in Mining (ICGCM) [1]. The ICGCM is a forum to promote closer communication among researchers, consultants, regulators, manufacturers, and mine operators to expedite solutions to ground control problems in mining [2], [3], [4], [5], [6], [7]. Fundamental research and advancements in ground control science define the central core of the conference mission. Providing information to mine operators is a priority, as the conference goal is to offer solutions-oriented information. In addition, the conference has included innovative technologies and ideas in mining-related fields such as exploration, geology, and surface and underground mining in all commodities. Many new ground control technologies and design standards adopted by the mining industry were first discussed at ICGCM. This conference is recognized as the leading international forum for introducing new ground-control-related research and products.

BACKGROUND: Sink drains in healthcare facilities may provide an environment for antimicrobial-resistant microorganisms, including carbapenemase-producing Klebsiella pneumoniae (CPKP). METHODS: We investigated the colonization of a biofilm consortia by CPKP in a model system simulating a sink-drain P-trap. Centers for Disease Control (CDC) biofilm reactors (CBRs) were inoculated with microbial consortia originally recovered from 2 P-traps collected from separate patient rooms (designated rooms A and B) in a hospital. Biofilms were grown on stainless steel (SS) or polyvinyl chloride (PVC) coupons in autoclaved municipal drinking water (ATW) for 7 or 28 days. RESULTS: Microbial communities in model systems (designated CBR-A or CBR-B) were less diverse than communities in respective P-traps A and B, and they were primarily composed of β and γ Proteobacteria, as determined using 16S rRNA community analysis. Following biofilm development CBRs were inoculated with either K. pneumoniae ST45 (ie, strain CAV1016) or K. pneumoniae ST258 KPC+ (ie, strain 258), and samples were collected over 21 days. Under most conditions tested (CBR-A: SS, 7-day biofilm; CBR-A: PVC, 28-day biofilm; CBR-B: SS, 7-day and 28-day biofilm; CBR-B: PVC, 28-day biofilm) significantly higher numbers of CAV1016 were observed compared to 258. CAV1016 showed no significant difference in quantity or persistence based on biofilm age (7 days vs 28 days) or substratum type (SS vs PVC). However, counts of 258 were significantly higher on 28-day biofilms and on SS. CONCLUSIONS: These results suggest that CPKP persistence in P-trap biofilms may be strain specific or may be related to the type of P-trap material or age of the biofilm.

BACKGROUND: The United States military regularly deploys thousands of service members throughout areas of South America and Africa that are endemic for yellow fever (YF) virus. To determine if booster doses might be needed for service members who are repetitively or continually deployed to YF endemic areas, we evaluated seropositivity among US military personnel receiving a single dose of YF vaccine based on time post-vaccination. METHODS: Serum antibodies were measured using a plaque reduction neutralization test with 50% cutoff in 682 military personnel at 5-39 years post-vaccination. We determined noninferiority of immune response by comparing the proportion seropositive among those vaccinated 10-14 years previously with those vaccinated 5-9 years previously. Noninferiority was supported if the lower-bound of the 2-tailed 95% CI for p(10-14years) - p(5-9years) was ≥-0.10. Additionally, the geometric mean antibody titer (GMT) at various timepoints following vaccination were compared to the GMT at 5-9 years. RESULTS: The proportion of military service members with detectable neutralizing antibodies 10-14 years after a single dose of YF vaccine (95.8%, 95% CI 91.2-98.1%) was non-inferior to the proportion 5-9 years after vaccination (97.8%, 95% CI 93.7-99.3%). Additionally, GMT among vaccine recipients at 10-14 years post vaccination (99, 95% CI 82-121) was non-inferior to GMT in YF vaccine recipients at 5-9 years post vaccination (115, 95% CI 96-139). The proportion of vaccinees with neutralizing antibodies remained high, and non-inferior, among those vaccinated 15-19 years prior (98.5%, 95%CI 95.5-99.7%). Although the proportion seropositive decreased among vaccinees ≥ 20 years post vaccination, >90% remained seropositive. CONCLUSIONS: Neutralizing antibodies were present in > 95% of vaccine recipients for at least 19 years after vaccination, suggesting that booster doses every 10 years are not essential for most U.S. military personnel.

Remdesivir is a broad-spectrum antiviral nucleotide prodrug that has been clinically evaluated in Ebola virus patients and recently received emergency use authorization (EUA) for treatment of COVID-19. With approvals from the Federal Select Agent Program and the Centers for Disease Control and Prevention's Institutional Biosecurity Board, we characterized the resistance profile of remdesivir by serially passaging Ebola virus under remdesivir selection; we generated lineages with low-level reduced susceptibility to remdesivir after 35 passages. We found that a single amino acid substitution, F548S, in the Ebola virus polymerase conferred low-level reduced susceptibility to remdesivir. The F548 residue is highly conserved in filoviruses but should be subject to specific surveillance among novel filoviruses, in newly emerging variants in ongoing outbreaks, and also in Ebola virus patients undergoing remdesivir therapy. Homology modeling suggests that the Ebola virus polymerase F548 residue lies in the F-motif of the polymerase active site, a region that was previously identified as susceptible to resistance mutations in coronaviruses. Our data suggest that molecular surveillance of this region of the polymerase in remdesivir-treated COVID-19 patients is also warranted.

BACKGROUND: Japanese encephalitis (JE) virus is an important cause of neurological disease in Asia. JE vaccine is recommended for travelers with higher JE risk itineraries. Inactivated Vero cell culture-derived JE vaccine (JE-VC) is the only JE vaccine currently available in the United States. An inactivated mouse brain-derived JE vaccine (JE-MB) previously was available but production was discontinued. One JE-VC dose administered to adults previously vaccinated with ≥3 doses of JE-MB provides good short-term protection for at least one month, but data on longer-term protection are limited. We evaluated non-inferiority of the JE virus neutralizing antibody response at 12-23 months in JE-MB-vaccinated adults administered one JE-VC dose compared with JE vaccine-naïve adults administered a JE-VC two-dose primary series. METHODS: We obtained archived sera from U.S. military personnel and performed a 50% plaque reduction neutralization test for anti-JE virus neutralizing antibodies. We compared the geometric mean titer (GMT) and seroprotection rate at 12-23 months after one JE-VC dose in previously JE-MB-vaccinated personnel and after the second JE-VC dose in previously JE vaccine-naïve personnel. Non-inferiority was concluded if the lower bound of the two-sided 95% confidence interval (CI) of the GMT ratio in previously vaccinated to vaccine-naïve personnel was >1/1.5. RESULTS: The GMT in previously JE-MB-vaccinated persons was 75 (95% CI 63-90) and in previously JE vaccine-naïve persons was 12 (95% CI 11-14), and seroprotection rates were 94% (235/250) and 54% (135/250), respectively. The ratio of GMTs was 6.3 (95% CI: 5.0-7.7), satisfying the criterion for non-inferiority. CONCLUSIONS: One JE-VC dose in previously JE-MB-vaccinated military personnel provides good protection for at least 1-2 years. The benefits of administration of a single JE-VC dose in previously JE-MB-vaccinated adults include a shorter time to completion of re-vaccination before travel, a decrease in the risk of adverse events, and reduced costs.