Human metapneumovirus (hMPV) is an important cause of respiratory illness. However, information about hMPV incidence, patient characteristics, and symptoms outside hospital settings is limited. During June 2022-March 2024, participants aged 6 months-49 years who were enrolled in the CASCADIA community-based cohort study submitted weekly illness surveys and nasal swabs, and completed follow-up illness surveys. Swabs collected 0-3 days before reporting new or worsening symptoms were tested for hMPV and other respiratory viruses by multiplex polymerase chain reaction. Incidence was analyzed using an exponential survival model. Among 3,549 participants, 306 had symptomatic hMPV infection, representing an average of 7.5 cases per 100 persons per year (95% CI = 6.7-8.4). Incidence was highest during January-March (adjusted hazard ratio [aHR] = 4.3; 95% CI = 3.0-6.0) compared with October-December, and among those aged 2-4 years (aHR = 5.8; 95% CI = 3.8-9.0) compared with those aged ≥40 years. The most frequently reported symptoms were cough (80.4%) and nasal congestion (71.9%). Among 252 (82.4%) participants who completed a post-illness follow-up survey, 68 (27.0%) missed work, school, or child care facility attendance. Together, these findings indicate that hMPV is a common cause of respiratory illness during late winter to spring, particularly among young children, and frequently disrupts daily activities. Understanding hMPV epidemiology can guide surveillance definitions, clinical testing, and prioritization of prevention strategies.

BACKGROUND: Household transmission of respiratory viruses may drive community spread. Few recent studies have examined household respiratory syncytial virus (RSV) transmission in the United States. METHODS: We conducted a prospective community-based cohort study from 1 June 2022 to 31 May 2023. Participants had blood samples collected and completed nasal swabs and surveys at least weekly, irrespective of symptoms. We tested serum for RSV antibody, nasal swabs by quantitative reverse transcription polymerase chain reaction (RT-qPCR), and performed whole genome sequencing. We evaluated secondary RSV transmission and associated risk factors based on a log-linear Poisson regression model. RESULTS: RSV was detected among 310 (10%) participants within 200 (20%) households. Most (94%) index cases were symptomatic. We identified 37 cases of potential secondary transmission within 14 days of a distinct index case (10%, 95% confidence interval [CI]: 7%, 14%); median age of index and secondary cases were 6 (interquartile range [IQR]: 3-10) and 35 (7-41) years, respectively, with 89% (24/27) of index cases aged 6 months to 12 years. Factors associated with increased risk of RSV transmission included index case viral detection ≥1 week and contact age ≤12 years. Of 120 sequenced specimens, the main lineages represented were A.d.5.2 (n = 37) and A.d.1 (n = 30). Sequenced viruses from households with ≥2 RSV infections were similar when occurring within ≤14 days (mean pairwise difference 4 [range 0-13], n = 17 households), compared to those >14 days (137 [37-236], n = 2). CONCLUSIONS: Most RSV household transmission occurs from infants and young children to adults. Viral genome sequencing demonstrated that multiple household infections within a 14-day period are likely due to within-household transmission.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States (US). RSV immunization, in the form of a monoclonal antibody (mAb) for infants and vaccines for pregnant people, may reduce infant RSV risk. METHODS: In April and May 2023, we surveyed adults with children in Oregon and Washington about the likelihood to accept infant mAb and maternal RSV vaccine and RSV awareness. We used multivariable logistic regression to identify predictors of self-reported likelihood of accepting RSV immunization. RESULTS: Among 1082 respondents, 68% and 70% responded they would very likely accept infant mAb or maternal RSV vaccine, respectively. Respondents had lower odds of accepting infant mAb (OR: 0.10, 95% CI: 0.07-0.15) and maternal RSV vaccine (OR: 0.16, 95% CI: 0.12-0.23) if they were somewhat or very concerned about side effects. Respondents had higher odds of accepting infant mAb if they received an influenza vaccination (OR: 3.79, 95% CI: 1.88-7.63). Respondents had higher odds of accepting maternal vaccine if they had an advanced degree (OR: 1.70, 95% CI: 1.06-2.73), had received an influenza vaccination (OR: 3.62, 95% CI: 1.80-7.25), or were aware of RSV before our survey (OR: 2.03, 95% CI: 1.03-4.01). CONCLUSION: Most respondents reported that they would likely accept RSV mAb for their infant or an RSV vaccine during pregnancy. Concerns about side effects lowered the odds of accepting immunization, however, nearly one-half of those concerned about side effects still expressed a high likelihood of accepting either immunization.

BACKGROUND: Institutions of higher education (IHE) have been a focus of SARS-CoV-2 transmission studies but there is limited information on how viral diversity and transmission at IHE changed as the pandemic progressed. METHODS: Here we analyze 3606 viral genomes from unique COVID-19 episodes collected at a public university in Seattle, Washington from September 2020 to September 2022. RESULTS: Across the study period, we found evidence of frequent viral transmission among university affiliates with 60% (n = 2153) of viral genomes from campus specimens genetically identical to at least one other campus specimen. Moreover, viruses from students were observed in transmission clusters at a higher frequency than in the overall dataset while viruses from symptomatic infections were observed in transmission clusters at a lower frequency. Although only a small percentage of community viruses were identified as possible descendants of viruses isolated in university study specimens, phylodynamic modeling suggested a high rate of transmission events from campus into the local community, particularly during the 2021-2022 academic year. CONCLUSIONS: We conclude that viral transmission was common within the university population throughout the study period but that not all university affiliates were equally likely to be involved. In addition, the transmission rate from campus into the surrounding community may have increased during the second year of the study, possibly due to return to in-person instruction.

BACKGROUND: Understanding protection against SARS-CoV-2 infection by vaccine and hybrid immunity is important for informing public health strategies as new variants emerge. METHODS: We analyzed data from three cohort studies spanning September 1, 2022-July 31, 2023, to estimate COVID-19 vaccine effectiveness (VE) against SARS-CoV-2 infection and symptomatic COVID-19 among adults with and without prior infection in the United States. Participants collected weekly nasal swabs, irrespective of symptoms, annual blood draws, and completed periodic surveys, which included vaccination status and prior infection history. Swabs were tested molecularly for SARS-CoV-2. VE was estimated using Cox proportional hazards models for the hazard ratios of infections, adjusting for covariates. VE was calculated considering prior infection and recency of vaccination. RESULTS: Among 3,344 adults, adjusted VE of bivalent vaccine against infection was 37.2% (95% CI: 12.3-55.7%) within 7-59 days of vaccination and 21.1% (95% CI: -0.5-37.1%) within 60-179 days of vaccination compared to participants who were unvaccinated/received an original monovalent vaccine dose ≥180 days prior. Overall, adjusted VE of bivalent vaccine against infection, in conjunction with prior infection, was 62.2% (95% CI: 46.0-74.5%) within 7-179 days of vaccination and 39.4% (95% CI: 12.5-61.6%) ≥180 days compared to naïve participants who were unvaccinated/received a monovalent vaccine dose ≥180 days prior. CONCLUSIONS: Adults with both prior infection and recent vaccination had high protection against infection and symptomatic illness. Recent vaccination alone provided moderate protection.

To understand how COVID-19 vaccines impact infection risk in children <5 years, we assessed risk of SARS-CoV-2 infection from Sept 2022-April 2023 in three cohort studies. There was no difference in risk by vaccination status. While vaccines reduce severe disease, they may not reduce SARS-CoV-2 infections in young children.

OBJECTIVE: The effects of sanitation and hygiene interventions on the gut microbiome and enteric pathogen burden are not well understood. We measured the association between free chlorine residue (FCR) levels in drinking water, microbiome composition, and stool enteric pathogens in infants and young children in Haiti. METHODS: FCR levels were measured in household drinking water and enteric pathogen burden was evaluated using multiplex RT-PCR of stool among 131 children from one month to five years of age living in Mirebalais, Haiti. Microbiome profiling was performed using metagenomic sequencing. RESULTS: Most individuals lived in households with undetectable FCR measured in the drinking water (112/131, 86%). Detection of enteric pathogen DNA in stool was common and did not correlate with household water FCR. The infant microbiome in households with detectable FCR demonstrated reduced richness (fewer total number of species, P=0.04 Kruskall-Wallis test) and less diversity by Inverse Simpson measures (P=0.05) than households with undetectable FCR. Infants in households with a detectable FCR were more likely to have abundant Bifidobacterium. Using in vitro susceptibility testing, we found that some Bifidobacterium species were resistant to chlorine. CONCLUSIONS: FCR in household drinking water did not correlate with enteric pathogen burden in our study.

BACKGROUND: SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. METHODS: This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). RESULTS: From February to December 2022, 5,757 participants reported 17,572 Ag-RDT results and completed 12,674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR-positive. Overall sensitivity and specificity were 53.0% (95% CI: 49.6-56.4%) and 98.8% (98.5-99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4 to 7 days post-symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥2 (68.5%) and ≥4 (75.8%) days after an initial Ag-RDT-negative result. CONCLUSION: Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high-risk for SARS-CoV-2 infection.

Vaccine effectiveness (VE) studies utilizing the test-negative design are typically conducted in clinical settings, rather than community populations, leading to bias in VE estimates against mild disease and limited information on VE in healthy young adults. In a community-based university population, we utilized data from a large SARS-CoV-2 testing program to estimate relative VE of COVID-19 mRNA vaccine primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection from September 2021 to July 2022. We used the test-negative design and logistic regression implemented via generalized estimating equations adjusted for age, calendar time, prior SARS-CoV-2 infection, and testing frequency (proxy for test-seeking behavior) to estimate relative VE. Analyses included 2,218 test-positive cases (59 % received monovalent booster dose) and 9,615 test-negative controls (62 %) from 9,066 individuals, with median age of 21 years, mostly students (71 %), White (56 %) or Asian (28 %), and with few comorbidities (3 %). More cases (23 %) than controls (6 %) had COVID-19-like illness. Estimated adjusted relative VE of primary series and monovalent booster dose versus primary series only against symptomatic SARS-CoV-2 infection was 40 % (95 % CI: 33-47 %) during the overall analysis period and 46 % (39-52 %) during the period of Omicron circulation. Relative VE was greater for those without versus those with prior SARS-CoV-2 infection (41 %, 34-48 % versus 33 %, 9 %-52 %, P < 0.001). Relative VE was also greater in the six months after receiving a booster dose (41 %, 33-47 %) compared to more than six months (27 %, 8-42 %), but this difference was not statistically significant (P = 0.06). In this relatively young and healthy adult population, an mRNA monovalent booster dose provided increased protection against symptomatic SARS-CoV-2 infection, overall and with the Omicron variant. University testing programs may be utilized for estimating VE in healthy young adults, a population that is not well-represented by routine VE studies.

BACKGROUND: College students are at increased risk for invasive meningococcal disease, but which students are most at risk is unclear. METHODS: US meningococcal disease cases in persons aged 18-24 years during 2014-2017 were included. Patients were classified as undergraduate students or other persons. Incidence in different student and non-student populations was compared. RESULTS: During 2014-2017, 229 meningococcal disease cases were reported in persons aged 18-24 years; 120 were in undergraduate students. Serogroup B accounted for 74% of cases in students. Serogroup B disease incidence was 4-fold higher in undergraduate students, 11.8-fold higher among first-year undergraduate students, and 8.6-fold higher among residence hall residents versus non-undergraduates. During outbreaks, students affiliated with Greek life had a 9.8-fold higher risk of disease compared to other students. A significantly higher party school ranking was observed for schools with sporadic or outbreak cases when compared to schools with no cases. CONCLUSIONS: The findings of increased disease risk among first-year students and those living on campus or affiliated with Greek life can inform shared clinical decision-making for serogroup B vaccines to prevent this rare but serious disease. These data also can inform school serogroup B vaccination policies and outbreak response measures.

Respiratory diphtheria is a serious infection caused by toxigenic Corynebacterium diphtheriae, and disease transmission mainly occurs through respiratory droplets. Between 2017 and 2019, a large diphtheria outbreak among forcibly displaced Myanmar nationals densely settled in Bangladesh was investigated. Here we utilized whole-genome sequencing (WGS) to characterize recovered isolates of C. diphtheriae and two co-circulating non-diphtheritic Corynebacterium (NDC) species - C. pseudodiphtheriticum and C. propinquum. C. diphtheriae isolates recovered from all 53 positive cases in this study were identified as toxigenic biovar mitis, exhibiting intermediate resistance to penicillin, and formed four phylogenetic clusters circulating among multiple refugee camps. Additional sequenced isolates collected from two patients showed co-colonization with non-toxigenic C. diphtheriae biovar gravis, one of which exhibited decreased susceptibility to the first-line antibiotics and harboured a novel 23-kb multidrug resistance plasmid. Results of phylogenetic reconstruction and virulence-related gene contents of the recovered NDC isolates indicated they were likely commensal organisms, though 80.4 %(45/56) were not susceptible to erythromycin, and most showed high minimum inhibition concentrations against azithromycin. These results demonstrate the high resolution with which WGS can aid molecular investigation of diphtheria outbreaks, through the quantification of bacterial genetic relatedness, as well as the detection of virulence factors and antibiotic resistance markers among case isolates.

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media.

CONTEXT: Between April 2020 and May 2021, the Centers for Disease Control and Prevention (CDC) awarded more than $40 billion to health departments nationwide for COVID-19 prevention and response activities. One of the identified priorities for this investment was improving infection prevention and control (IPC) in nursing homes. PROGRAM: CDC developed a virtual course to train new and less experienced public health staff in core healthcare IPC principles and in the application of CDC COVID-19 healthcare IPC guidance for nursing homes. IMPLEMENTATION: From October 2020 to August 2021, the CDC led training sessions for 12 cohorts of public health staff using pretraining reading materials, case-based scenarios, didactic presentations, peer-learning opportunities, and subject matter expert-led discussions. Multiple electronic assessments were distributed to learners over time to measure changes in self-reported knowledge and confidence and to collect feedback on the course. Participating public health programs were also assessed to measure overall course impact. EVALUATION: Among 182 enrolled learners, 94% completed the training. Most learners were infection preventionists (42%) or epidemiologists (38%), had less than 1 year of experience in their health department role (75%), and had less than 1 year of subject matter experience (54%). After training, learners reported increased knowledge and confidence in applying the CDC COVID-19 healthcare IPC guidance for nursing homes (≥81%) with the greatest increase in performing COVID-19 IPC consultations and assessments (87%). The majority of participating programs agreed that the course provided an overall benefit (88%) and reduced training burden (72%). DISCUSSION: The CDC's virtual course was effective in increasing public health capacity for COVID-19 healthcare IPC in nursing homes and provides a possible model to increase IPC capacity for other infectious diseases and other healthcare settings. Future virtual healthcare IPC courses could be enhanced by tailoring materials to health department needs, reinforcing training through applied learning experiences, and supporting mechanisms to retain trained staff.

This report describes the complete genome sequences of four isolates of the nondiphtheritic Corynebacterium (NDC) species Corynebacterium pseudodiphtheriticum and Corynebacterium propinquum, recovered during investigation of a large diphtheria outbreak in Bangladesh. These data will assist in better delineating the boundary between these related species and understanding their virulence potential.

BACKGROUND: Previous SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined ("hybrid immunity"), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the U.S. population that have been infected, vaccinated, or with hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. METHODS: In this serial cross-sectional study, nationwide blood donor specimens collected during January-December 2021 were tested for spike and nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population, and were compared temporally and by demographic factors. RESULTS: Overall, 1,123,855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity due to: vaccination without previous infection increased from 3.5% (95% CI, 3.4%-3.7%) to 64.0%, (95% CI, 63.5%-64.5%); previous infection without vaccination decreased from 15.6% (95% CI, 15.2%-16.0%) to 11.7% (95% CI, 11.4%-12.0%); hybrid immunity increased from 0.7% (95% CI, 0.6%-0.7%) to 18.9% (95% CI, 18.5%-19.3%); and from infection, vaccination, or both increased from 19.8% (95% CI (19.3-20.2) to 94.5% (95% CI, 93.5%-94.0% 0.1%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by gender. CONCLUSIONS: Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts.

This article is a compilation of summaries prepared by lead investigators for large-scale safety and efficacy studies on mass drug administration of IDA (ivermectin, diethylcarbamazine, and albendazole) for lymphatic filariasis. The summaries highlight the experiences of study teams that assessed the safety and efficacy of IDA in five countries: India, Indonesia, Haiti, Papua New Guinea, and Fiji. They also highlight significant challenges encountered during these community studies and responses to those challenges that contributed to success.

A key component to achieving the global goal of elimination of lymphatic filariasis (LF) is the availability of appropriate tools for disease mapping, monitoring, and surveillance. However, the development of these tools for a neglected disease such as LF can be a challenge. The lack of a commercial market and low familiarity with these diseases leave little incentive for diagnostic manufacturers to invest in this space. The Filarial Test Strip (FTS) development story provides a case study on how a multi-stakeholder, public-private partnership model facilitated the development, evaluation, and introduction of a new monitoring and surveillance tool for LF. This paper will reflect on the experience with the FTS and document the process from development of the target product profile to adoption and scale-up in country programs. Lessons learned from both the successes and challenges experienced during this process may help inform future efforts to develop and introduce new diagnostic or surveillance tools for neglected diseases.

BACKGROUND: Nursing homes (NHs) provide care in a congregate setting for residents at high risk of severe outcomes from SARS-CoV-2 infection. In spring 2020, NHs were implementing new guidance to minimize SARS-CoV-2 spread among residents and staff. OBJECTIVE: To assess whether telephone and video-based infection control assessment and response (TeleICAR) strategies could efficiently assess NH preparedness and help resolve gaps. DESIGN: We incorporated Centers for Disease Control and Prevention COVID-19 guidance for NH into an assessment tool covering 6 domains: visitor restrictions; health care personnel COVID-19 training; resident education, monitoring, screening, and cohorting; personal protective equipment supply; core infection prevention and control (IPC); and communication to public health. We performed TeleICAR consultations on behalf of health departments. Adherence to each element was documented and recommendations provided to the facility. SETTING AND PARTICIPANTS: Health department-referred NHs that agreed to TeleICAR consultation. METHODS: We assessed overall numbers and proportions of NH that had not implemented each infection control element (gap) and proportion of NH that reported making ≥1 change in practice following the assessment. RESULTS: During April 13 to June 12, 2020, we completed TeleICAR consultations in 629 NHs across 19 states. Overall, 524 (83%) had ≥1 implementation gaps identified; the median number of gaps was 2 (interquartile range: 1-4). The domains with the greatest number of facilities with gaps were core IPC practices (428/625; 68%) and COVID-19 education, monitoring, screening, and cohorting of residents (291/620; 47%). CONCLUSIONS AND IMPLICATIONS: TeleICAR was an alternative to onsite infection control assessments that enabled public health to efficiently reach NHs across the United States early in the COVID-19 pandemic. Assessments identified widespread gaps in core IPC practices that put residents and staff at risk of infection. TeleICAR is an important strategy that leverages infection control expertise and can be useful in future efforts to improve NH IPC.

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools.

Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox's Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April-May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

OBJECTIVE: to describe a pilot infection prevention and control (IPC) assessment conducted in skilled nursing facilities (SNFs) in New York State (NYS) during a pivotal two-week period when the region became the nation's epicenter for COVID-19. DESIGN: a telephone and video assessment of IPC measures in SNFs at high risk or experiencing COVID-19 activity. PARTICIPANTS: SNFs in 14 NYS counties including New York City. INTERVENTION: a three-component remote IPC assessment: 1) screening tool; 2) telephone IPC checklist; and 3) COVID-19 video IPC assessment ("COVIDeo"). RESULTS: 92 SNFs completed the IPC screening tool and checklist; 52/92 (57%) were conducted as part COVID-19 investigations, and 40/92 (43%) were proactive prevention-based assessments. Among the 40 proactive assessments, 14/40 (35%) identified suspected or confirmed COVID-19 cases. COVIDeo was performed in 26/92 (28%) of assessments and provided observations that other tools would have missed including: PPE (personal protective equipment) that was not easily accessible, redundant, or improperly donned, doffed, or stored and specific challenges implementing IPC in specialty populations. The IPC assessments took approximately one hour each, reached an estimated four times as many SNFs as onsite visits in a similar timeframe. CONCLUSIONS: Remote IPC assessments by telephone and video provided a timely and feasible method to assess the extent to which IPC interventions had been implemented in a vulnerable setting and to disseminate real-time recommendations. Remote assessments are now being implemented across NYS and in various healthcare facility types. Similar methods have been adapted nationally through CDC.

BACKGROUND: Many countries will not reach elimination targets for lymphatic filariasis in 2020 using the two-drug treatment regimen (diethylcarbamazine citrate [DEC] and albendazole [DA]). A cluster-randomized, community-based safety study performed in Fiji, Haiti, India, Indonesia and Papua New Guinea tested the safety and efficacy of a new regimen of ivermectin, DEC and albendazole (IDA). METHODOLOGY/PRINCIPAL FINDINGS: To assess acceptability of IDA and DA, a mixed methods study was embedded within this community-based safety study. The study objective was to assess the acceptability of IDA versus DA. Community surveys were performed in each country with randomly selected participants (>14 years) from the safety study participant list in both DA and IDA arms. In depth interviews (IDI) and focus group discussions (FGD) assessed acceptability-related themes. In 1919 individuals, distribution of sex, microfilariae (Mf) presence and circulating filarial antigenemia (CFA), adverse events (AE) and age were similar across arms. A composite acceptability score summed the values from nine indicators (range 9-36). The median (22.5) score indicated threshold of acceptability. There was no difference in scores for IDA and DA regimens. Mean acceptability scores across both treatment arms were: Fiji 33.7 (95% CI: 33.1-34.3); Papua New Guinea 32.9 (95% CI: 31.9-33.8); Indonesia 30.6 (95% CI: 29.8-31.3); Haiti 28.6 (95% CI: 27.8-29.4); India 26.8 (95% CI: 25.6-28) (P<0.001). AE, Mf or CFA were not associated with acceptability. Qualitative research (27 FGD; 42 IDI) highlighted professionalism and appreciation for AE support. No major concerns were detected about number of tablets. Increased uptake of LF treatment by individuals who had never complied with MDA was observed. CONCLUSIONS/SIGNIFICANCE: IDA and DA regimens for LF elimination were highly and equally acceptable in individuals participating in the community-based safety study in Fiji, Haiti, India, Indonesia, and Papua New Guinea. Country variation in acceptability was significant. Acceptability of the professionalism of the treatment delivery was highlighted.

BACKGROUND: Diphtheria, a life-threatening respiratory disease, is caused mainly by toxin-producing strains of Corynebacterium diphtheriae, while nontoxigenic Corynebacteria, such as C. pseudodiphtheriticum rarely causes diphtheria-like illness. Recently several global diphtheria outbreaks have resulted from the breakdown of healthcare infrastructures particularly in countries experiencing political conflict. This report summarizes a laboratory and epidemiological investigation of a diphtheria outbreak among Forcibly Displaced Myanmar Nationals in Bangladesh. METHODS: Specimens and clinical information were collected from patients presenting at Diphtheria Treatment Centers. Swabs were tested for toxin-gene (tox) bearing C. diphtheriae by real-time (RT) PCR and culture. The isolation of another Corynebacterium species prompted further laboratory investigation. RESULTS: Among 382 patients; 153 (40%) tested tox-positive for C. diphtheriae by RT-PCR; 31 (20%) PCR-positive swabs were culture-confirmed. RT-PCR revealed 78% (298/382) of patients tested positive for C. pseudodiphtheriticum. Of patients positive for only C. diphtheriae, 63% (17/27) had severe disease compared to 55% (69/126) positive for both Corynebacterium species, and 38% (66/172) for only C. pseudodiphtheriticum. CONCLUSIONS: We report the confirmation of a diphtheria outbreak and identification of a co-circulating Corynebacterium species. The high proportion of C. pseudodiphtheriticum co-detection may explain why many suspected patients testing negative for C. diphtheriae presented with diphtheria-like symptoms.

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.

BACKGROUND: During August 2017-January 2018, more than 700,000 forcibly displaced Rohingyas crossed into Cox's Bazar, Bangladesh. In response to measles and diphtheria cases, first documented in September and November 2017, respectively, vaccination campaigns targeting children <15 years old were mobilized during September 2017-March 2018. However, in a rapidly evolving emergency situation, poor sanitation, malnutrition, overcrowding, and lack of access to safe water and healthcare can increase susceptibility to infectious diseases, particularly among children. We aimed to estimate population immunity to vaccine-preventable diseases (VPDs) after vaccination activities in the camps to identify any remaining immunity gaps among Rohingya children. METHODS AND FINDINGS: We conducted a cross-sectional serologic and vaccination coverage survey in Nayapara Registered Refugee Camp ("Nayapara") and makeshift settlements (MSs) April 28, 2018 to May 31, 2018, among 930 children aged 6 months to 14 years. MSs are informal, self-settled areas with a population of more than 850,000, the majority of whom arrived after August 2017, whereas Nayapara is a registered camp and has better infrastructure than MSs, including provision of routine immunization services. Households were identified using simple random sampling (SRS) in Nayapara and multistage cluster sampling in MSs (because household lists were unavailable). Dried blood spots (DBSs) were collected to estimate seroprotection against measles, rubella, diphtheria, and tetanus, using Luminex multiplex bead assay (MBA). Caregiver interviews assessed vaccination campaign participation using vaccination card or recall. In Nayapara, 273 children aged 1 to 6 years participated; 46% were female and 88% were registered refugees. In MSs, 358 children aged 1 to 6 years and 299 children aged 7 to 14 years participated; 48% of all children in MSs were female, and none were registered refugees. In Nayapara, estimated seroprotection among 1- to 6-year-olds was high for measles, rubella, diphtheria, and tetanus (91%-98%; 95% confidence interval [CI] 87%-99%); children >6 years were not assessed. In MSs, measles seroprotection was similarly high among 1- to 6-year-olds and 7- to 14-year-olds (91% [95% CI 86%-94%] and 99% [95% CI 96%-100%], respectively, p < 0.001). Rubella and diphtheria seroprotection in MSs were significantly lower among 1- to 6-year-olds (84% [95% CI 79%-88%] and 63% [95% CI 56%-70%]) compared to 7- to 14-year-olds (96% [95% CI 90%-98%] and 77% [95% CI 69%-84%]) (p < 0.001). Tetanus seroprevalence was similar among 1- to 6-year-olds and 7- to 14-year-olds (76% [95% CI 69%-81%] and 84% [95% CI 77%-89%], respectively; p = 0.07). Vaccination campaign coverage was consistent with seroprotection in both camps. However, nonresponse, the main limitation of the study, may have biased the seroprotection and campaign coverage results. CONCLUSIONS: In this study, we observed that despite multiple vaccination campaigns, immunity gaps exist among children in MSs, particularly for diphtheria, which requires serial vaccinations to achieve maximum protection. Therefore, an additional tetanus-diphtheria campaign may be warranted in MSs to address these remaining immunity gaps. Rapid scale-up and strengthening of routine immunization services to reach children and to deliver missed doses to older children is also critically needed to close immunity gaps and prevent future outbreaks.

BACKGROUND: The World Health Organization (WHO) currently recommends height or age-based dosing as alternatives to weight-based dosing for mass drug administration lymphatic filariasis (LF) elimination programs. The goals of our study were to compare these alternative dosing strategies to weight-based dosing and to develop and evaluate new height-based dosing pole scenarios. METHODOLOGY/PRINCIPAL FINDINGS: Age, height and weight data were collected from >26,000 individuals in five countries during a cluster randomized LF clinical trial. Weight-based dosing for diethylcarbamazine (DEC; 6 mg/kg) and ivermectin (IVM; 200 ug/kg) with tablet numbers derived from a table of weight intervals was treated as the "gold standard" for this study. Following WHO recommended age-based dosing of DEC and height-based dosing of IVM would have resulted in 32% and 27% of individuals receiving treatment doses below those recommended by weight-based dosing for DEC and IVM, respectively. Underdosing would have been especially common in adult males, who tend to have the highest LF prevalence in many endemic areas. We used a 3-step modeling approach to develop and evaluate new dosing pole cutoffs. First, we analyzed the clinical trial data using quantile regression to predict weight from height. We then used weight predictions to develop new dosing pole cutoff values. Finally, we compared different dosing pole cutoffs and age and height-based WHO dosing recommendations to weight-based dosing. We considered hundreds of scenarios including country- and sex-specific dosing poles. A simple dosing pole with a 6-tablet maximum for both DEC and IVM reduced the underdosing rate by 30% and 21%, respectively, and was nearly as effective as more complex pole combinations for reducing underdosing. CONCLUSIONS/SIGNIFICANCE: Using a novel modeling approach, we developed a simple dosing pole that would markedly reduce underdosing for DEC and IVM in MDA programs compared to current WHO recommended height or age-based dosing.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. METHODS AND FINDINGS: Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 mug/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were >/=5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. CONCLUSIONS: In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02899936.

On December 12, 2018, an immunocompromised man with non-Hodgkin’s lymphoma, aged 73 years, was evaluated by an ophthalmologist for left eyelid redness, swelling, and eye discharge and received a diagnosis of ligneous (pseudomembranous) conjunctivitis. The pseudomembrane was debrided and sent for culture, and the patient was prescribed oral amoxicillin clavulanate and moxifloxacin eye drops, with topical loteprednol and cyclosporine to decrease the robust inflammatory response. Corynebacterium ulcerans, one of three species of Corynebacterium (in addition to C. diphtheriae and C. psuedotuberculosis) that can harbor the diphtheria toxin–producing gene was initially identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry performed on an isolate obtained from culture of the pseudomembrane at a Missouri hospital on December 13. The Missouri Department of Health and Senior Services (MDHSS) laboratory-confirmed C. ulcerans by culture and forwarded the isolate to CDC for toxin testing. On December 28, CDC confirmed toxin-producing C. ulcerans. The patient had no systemic symptoms, was not hospitalized, and did not receive diphtheria antitoxin. On January 11, 2019, following multiple membrane removals and no residual membrane; cultures of conjunctival swabs tested by the hospital were negative for C. ulcerans. The patient was not up-to-date for tetanus-diphtheria (Td) vaccine and had postponed vaccination because of his ongoing cancer treatment.

Meningococcal disease is a rare, but serious, bacterial infection that progresses rapidly and can be life-threatening, even with prompt antibiotic treatment. Men who have sex with men (MSM) have previously been reported to be at increased risk for meningococcal disease compared with other men, and recent outbreaks of serogroup C meningococcal disease among MSM have occurred (1). However, the epidemiology of meningococcal disease among MSM in the United States is not well described, in part, because information about MSM has not historically been collected as part of routine meningococcal disease surveillance. To better characterize and identify risk factors for meningococcal disease in general, supplementary data and isolates have been collected since 2015 through enhanced meningococcal disease surveillance activities. During 2015-2016, 271 cases of meningococcal disease in men aged >/=18 years were reported to the National Notifiable Diseases Surveillance System (NNDSS) in 45 states participating in this enhanced surveillance. Forty-eight (17.7%) cases were in men identified as MSM, including 17 (37.8%) with human immunodeficiency virus (HIV) infection. Among MSM, 39 (84.8%) cases were caused by Neisseria meningitidis serogroup C, whereas this serogroup was responsible for only 16.4% of cases among men who were not known to be MSM (non-MSM). Despite improvements in surveillance, MSM likely remain underascertained among men with meningococcal disease. Improved surveillance data are needed to understand the prevalence of and risk for meningococcal disease among MSM and inform policy and prevention strategies. Vaccination with quadrivalent meningococcal conjugate (MenACWY) vaccine is recommended for the control of meningococcal disease outbreaks caused by serogroups A, C, W, or Y, including during outbreaks among MSM; in addition, all persons aged >/=2 months with HIV infection should receive MenACWY vaccine because of the increased risk for meningococcal disease.