Accurate rapid diagnostic tests (RDTs) are needed to diagnose lymphatic filariasis (LF) in global elimination programmes. We evaluated the performance of the new STANDARD Q Filariasis Antigen Test (QFAT) against the Bioline Filariasis Test Strip (FTS) for detecting W. bancrofti antigen (Ag) in laboratory conditions, using serum (n = 195) and plasma (n = 189) from LF-endemic areas (Samoa, American Samoa and Myanmar) and Australian negative controls (n = 46). The prior Ag status of endemic samples (54.9% Ag-positive) was determined by rapid test (ICT or FTS) or Og4C3 ELISA. The proportion of samples testing positive at 10 min was similar for QFAT (44.8%) and FTS (41.3%). Concordance between tests was 93.5% (kappa 0.87, n = 417) at 10 min, and it increased to 98.8% (kappa 0.98) at 24 h. The sensitivities of QFAT and FTS at 10 min compared to the prior results were 92% (95% CI 88.0-96.0) and 86% (95% CI 80.0-90.0), respectively, and they increased to 97% and 99% at 24 h. Specificity was 98% for QFAT and 99% for FTS at 10 min. Both tests showed evidence of cross-reaction with Dirofilaria repens and Onchocerca lupi but not with Acanthochilonema reconditum or Cercopithifilaria bainae. Under laboratory conditions, QFAT is a suitable alternative RDT to FTS.

Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and prevalence among US children aged 0-17 years between 2000 and 2021 by cause, child age, race and ethnicity, sex of deceased parent and state, and also accounted for grandparent caregiver loss using population survey data. In 2021, we estimate that 2.91 million children (4.2% of children) had in their lifetime experienced prevalent orphanhood and caregiver death combined, with incidence increasing by 49.5% and prevalence by 7.9% since 2000. Populations disproportionately affected by orphanhood included 5.2% of all adolescents; 6.4% and 4.7%, respectively, of non-Hispanic American Indian or Alaska Native, and non-Hispanic Black children; and children in southern and eastern states. In 2021, drug overdose was the leading cause of orphanhood among non-Hispanic white children, but not among minoritized subgroups. Effective policies and programs to support nearly three million bereaved children are needed to reduce the acute and long-term negative effects of orphanhood.

BACKGROUND: Coccidioidomycosis is a fungal infection that poses a serious risk when transmitted through organ transplantation. We analyzed cases reported to the Organ Procurement and Transplantation Network ad hoc Disease Transmission Advisory Committee from 2013 to 2022. METHODS: Donors and/or recipients who had positive Coccidioides immitis/posadasii serology, pathology, and/or culture were included in this study. Cases adjudicated as 'proven' or 'probable' were analyzed for donor infection risk factors, the timing of infection, transmission by organ type, clinical manifestations, and recipient outcomes. Patient and facility identifiers were removed prior to review. RESULTS: During this time period, 73 potential instances of Coccidioides donor disease transmission events were reported. Among them, infection was transmitted from seven deceased donors to eight recipients. All seven deceased donors had prior infection or exposure to regions where coccidioidomycosis is endemic. Of 20 individuals receiving organs from these donors, eight developed infection, resulting in a 40% transmission rate. The median time to diagnosis post-transplant was 39 days. Disseminated disease occurred in six recipients, five of whom died from the infection. Notably, none of the recipients who received prophylactic antifungal treatment died from the infection. CONCLUSION: Despite its rarity, donor-derived Coccidioides infection is a serious concern, particularly due to the high mortality rate in the early post-transplant period. To mitigate these risks, a thorough assessment of donor exposure history, coupled with donor serology and bronchoalveolar lavage cultures, can effectively guide post-transplant antifungal prophylaxis. Prompt reporting is crucial to prevent Coccidioides infections among other recipients.

BACKGROUND: To monitor the progress of lymphatic filariasis (LF) elimination programmes, field surveys to assess filarial antigen (Ag) prevalence require access to reliable, user-friendly rapid diagnostic tests. We aimed to evaluate the performance of the new Q Filariasis Antigen Test (QFAT) with the currently recommended Filariasis Test Strip (FTS) for detecting the Ag of Wuchereria bancrofti, the causative agent of LF, under field laboratory conditions. METHODOLOGY/PRINCIPAL FINDINGS: During an LF survey in Samoa, 344 finger-prick blood samples were tested using FTS and QFAT. Microfilariae (Mf) status was determined from blood slides prepared from any sample that reported Ag-positive by either Ag-test. Each test was re-read at 1 hour and the next day to determine the stability of results over time. Overall Ag-positivity by FTS was 29.0% and 30.2% by QFAT. Concordance between the two tests was 93.6% (kappa = 0.85). Of the 101 Mf slides available, 39.6% were Mf-positive, and all were Ag-positive by both tests. Darker test line intensities from Ag-positive FTS were found to predict Mf-positivity (compared to same/lighter line intensities). QFAT had significantly higher reported test result changes than FTS, mostly reported the next day, but fewer changes were reported between 10 minutes to 1-hour. The field laboratory team preferred QFAT over FTS due to the smaller blood volume required, better usability, and easier readability. CONCLUSION/SIGNIFICANCE: QFAT could be a suitable and user-friendly diagnostic alternative for use in the monitoring and surveillance of LF in field surveys based on its similar performance to FTS under field laboratory conditions.

Background: Free-living amoebas (FLAs) can cause severe and fatal central nervous system infections that are difficult to diagnose. Methods: We present the case of a 74-year-old immunocompetent woman admitted for focal neurological symptoms with enhancing lesions in the right cerebellar hemisphere. A first cerebral biopsy showed granulomatous inflammation, but no microorganisms were identified. After transient clinical improvement, she eventually deteriorated 4 months after initial presentation, with an MRI confirming multiple new masses affecting all cerebral lobes. Results: A second brain biopsy revealed granulomatous and acute inflammation with organisms containing a large central nucleus with prominent karyosome, consistent with FLAs. Immunohistochemical and polymerase chain reaction assays performed at CDC were positive for Acanthamoeba spp, confirming the diagnosis of granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. The patient was treated with combination therapy recommended by CDC, but died a few days later. Upon histopathological rereview, amoebic cysts and trophozoites were identified by histochemical and immunohistochemical methods in the first cerebral biopsy. Conclusion: FLA infections can be challenging to diagnose because of the low incidence, non-specific clinical and radiological presentation, lack of accessible diagnostic tools, and clinicians' unfamiliarity. This case highlights the importance of recognizing FLA as a potential cause of granulomatous encephalitis, even in the absence of risk factors, as early treatment might be associated with favourable outcomes in case reports. When suspected, CDC laboratories offer tests to confirm the diagnosis promptly. | Historique : Les amibes libres peuvent causer des infections du système nerveux central graves et fatales qui sont difficiles à diagnostiquer. Méthodologie : Les auteurs présentent le cas d'une femme immunocompétente de 74 ans hospitalisée à cause de symptômes neurologiques focaux avec lésions rehaussantes dans l'hémisphère cérébelleux droit. Une première biopsie cérébrale a révélé une inflammation granulomateuse, mais aucun microorganisme n'a été décelé. Après une amélioration clinique transitoire, son état s'est détérioré quatre mois après la première consultation, et l'IRM a confirmé de multiples nouvelles masses touchant tous les lobes cérébraux. Résultats : Une deuxième biopsie cérébrale a révélé une inflammation granulomateuse aiguë par des organismes dont les gros noyaux centraux et les caryosomes volumineux étaient évocateurs d'amibes libres. L'immunohistochimie et l'amplification en chaîne par polymérase effectuées aux CDC se sont avérés positives pour Acanthamoeba spp, ce qui a confirmé un diagnostic d'encéphalite amibienne granulomateuse causée par Acanthamoeba spp. La patiente a reçu une polythérapie recommandée par les CDC, mais est malheureusement décédée quelques jours plus tard. À la reprise de l'analyse histopathologique, des kystes amibiens et des trophozoïtes ont été décelés dans la première biopsie cérébrale par des méthodes histochimiques et immunohistochimiques. Conclusion : Les infections par des amibes libres peuvent être difficiles à diagnostiquer en raison de leur faible incidence, de leur présentation clinique et radiologique non spécifique, de l'absence d'outils diagnostiques accessibles et de la méconnaissance des cliniciens. Ce cas renforce l'importance d'inclure les amibes libres dans les causes potentielles d'encéphalite granulomateuse, même en l'absence de facteurs de risque, car un traitement rapide a été associé à des résultats favorables dans certains rapports de cas. Lorsqu'on en soupçonne la présence, les laboratoires des CDC offrent des tests pour confirmer rapidement le diagnostic.

We determined the in vitro minimum lethal concentration (MLC) of secnidazole (SEC) and assessed correlation with clinical susceptibility among T. vaginalis isolates obtained from 71 women, of whom 66 were successfully treated with this medication. An MLC ≤12.5 μg/ml correlated with clinical susceptibility in this study.

As neglected tropical disease programs rely on participation in rounds of mass drug administration (MDA), there is concern that individuals who have never been treated could contribute to ongoing transmission, posing a barrier to elimination. Previous research has suggested that the size and characteristics of the never-treated population may be important but have not been sufficiently explored. To address this critical knowledge gap, four meetings were held from December 2020 to May 2021 to compile expert knowledge on never treatment in lymphatic filariasis (LF) MDA programs. The meetings explored four questions: the number and proportion of people never treated, their sociodemographic characteristics, their infection status and the reasons why they were not treated. Meeting discussions noted key issues requiring further exploration, including how to standardize measurement of the never treated, adapt and use existing tools to capture never-treated data and ensure representation of never-treated people in data collection. Recognizing that patterns of never treatment are situation specific, participants noted measurement should be quick, inexpensive and focused on local solutions. Furthermore, programs should use existing data to generate mathematical models to understand what levels of never treatment may compromise LF elimination goals or trigger programmatic action.

Background Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Here, we explore the potential of targeted strategies to strengthen post-MDA surveillance.Methodology/Principal Findings Using Ag data plus new antibody data (Wb123, Bm14, Bm33) from the 2016 surveys, we identified risk factors for seropositivity using multivariable logistic regression. We compared TAS with strategies that targeted high-risk subpopulations (older ages, householders of Ag-positive TAS children [index children]) and/or known hotspots, and used NNTestav (average number needed to test to identify one positive) to compare sampling efficiency.Antibody prevalence in TAS-3 (n=1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n=2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of index children. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali’i (aOR 15.81), and outdoor workers (aOR 2.61). Using Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies.Conclusions/Significance We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS), followed by targeted strategies in subgroups and locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. The utility of antibodies in surveillance should also be explored.AUTHOR SUMMARY Lymphatic filariasis (LF) is a parasitic infection transmitted by mosquito bites. Globally, tens of millions are infected, with many disfigured and disabled by severe damage to their lymphatic systems, such as severe swelling of the legs (elephantiasis) or scrotum (hydrocele). The Global Programme to Eliminate LF (GPELF) aims to interrupt disease transmission through mass drug administration (MDA), and to control illness and suffering in affected persons. The World Health Organization recommends conducting Transmission Assessment Surveys (TAS) in school children aged 6 to 7 years, to determine if infection rates have dropped to levels where disease transmission is no longer sustainable. From 2000-2006, American Samoa conducted MDA and made significant progress towards eliminating LF. However, despite passing TAS in 2011/2012 and 2015, surveys in 2016 showed evidence of resurgence. Our study explored alternative surveillance strategies and compared their efficiency with TAS. Based on our findings, we recommended that in addition to TAS, strategies that target high-risk populations and hotspots would strengthen surveillance and help countries achieve their goals of LF elimination.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work received financial support from the Coalition for Operational Research on Neglected Tropical Diseases (COR-NTD), which is funded at The Task Force for Global Health primarily by the Bill & Melinda Gates Foundation [OPP1053230], the United Kingdom Department for International Development, and by the United States Agency for International Development through its Neglected Tropical Diseases Program. CLL was supported by an Australian National Health and Medical Research Council Fellowship (1109035). MS was supported by a fellowship funded by the Westpac Scholars Trust. The funders had no role in study design, data collection and analysis, decisi n to publish, or preparation of the manuscript.Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe datasets generated and analysed during the present study are available from the corresponding author upon reasonable request.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. 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.

Objectives Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. Methods We examined school-level Ag and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). Conclusion Anti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for T. vaginalis isolates obtained from women who had failed treatment (n = 4) or were successfully cured (n = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive T. vaginalis isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more T. vaginalis isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains.

Mozambique introduced guidelines for integrated gender-based violence (GBV) services in 2012. In 2017, we trained providers on empathetic and supportive services to GBV survivors and introduced home-based services for survivors who are loss-to-follow up. Rate ratios of clinic visits were compared before and after intervention initiation, using exact significance tests. Data of 1,806 GBV survivors were reviewed, with a total of 2005 events. The median age was 23 years (IQR 17-30) and 89% were women. Among those reporting violence, 69% reported physical violence, 18% reported sexual violence (SV), and 12% reported psychological violence. Rates of care-seeking behavior were higher in the intervention period (rate ratio 1.31 [95%CI: 1.18-1.46]); p < 0.01. Among those eligible for post-exposure prophylaxis (PEP), 94% initiated PEP. Uptake of HIV retesting improved in percentage points by 34% (14% to 48%), 34% (8% to 42%) and 26% (5% to 31%) at 1-, 3- and 6-months, respectively. The intervention led to an increase in the rate of GBV survivors seeking health care services, and improved rates of follow-up care among SV survivors initiating PEP. Strengthening of PEP adherence counseling remains crucial for improving GBV services.

OBJECTIVES: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. METHODS: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. RESULTS: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). CONCLUSION: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-mass drug administration (MDA) surveillance and decision making should be further investigated in other settings.

In 2015, the Sierra Leone Ministry of Health and Sanitation (MoHS) and the Centers for Disease Control and Prevention (CDC) agreed to consolidate data recorded by MoHS and international partners during the Ebola epidemic and create the Sierra Leone Ebola Database (SLED). The primary objectives were helping families to identify the location of graves of their loved ones who died from any cause at the time of the Ebola epidemic and creating a data source for epidemiological research. The Family Reunification Program fulfils the first SLED objective. The purpose of this paper is to describe the Family Reunification Program (Program) development, functioning and results. The MoHS, CDC, SLED Team, and Concern Worldwide developed, tested, and implemented methodology and tools to conduct the Program. Family liaisons were trained in protection of the personally identifiable information. The SLED Family Reunification Program allows families in Sierra Leone, who did not know the final resting place of their loved ones, to be reunited with their graves and to bring them relief and closure. Continuing family requests in search of the burial place of loved ones five years after the end of the epidemic shows that the emotional burden of losing a family member and not knowing the place of burial does not diminish with time. As of February 2021, the Program continues and is described to allow its replication for other emergency events including COVID-19 and new Ebola outbreaks.

BACKGROUND: During the 2014-2016 Ebola outbreak in West Africa, the Sierra Leone Ministry of Health and Sanitation (MoHS), the US Centers for Disease Control and Prevention, and responding partners under the coordination of the National Ebola Response Center (NERC) and the MoHS's Emergency Operation Center (EOC) systematically recorded information from the 117 Call Center system and district alert phone lines, case investigations, laboratory sample testing, clinical management, and safe and dignified burial records. Since 2017, CDC assisted MoHS in building and managing the Sierra Leone Ebola Database (SLED) to consolidate these major data sources. The primary objectives of the project were helping families to identify the location of graves of their loved ones who died at the time of the Ebola epidemic through the SLED Family Reunification Program and creating a data source for epidemiological research. The objective of this paper is to describe the process of consolidating epidemic records into a useful and accessible data collection and to summarize data characteristics, strength, and limitations of this unique information source for public health research. METHODS: Because of the unprecedented conditions during the epidemic, most of the records collected from responding organizations required extensive processing before they could be used as a data source for research or the humanitarian purpose of locating burial sites. This process required understanding how the data were collected and used during the outbreak. To manage the complexity of processing the data obtained from various sources, the Sierra Leone Ebola Database (SLED) Team used an organizational strategy that allowed tracking of the data provenance and lifecycle. RESULTS: The SLED project brought raw data into one consolidated data collection. It provides researchers with secure and ethical access to the SLED data and serves as a basis for the research capacity building in Sierra Leone. The SLED Family Reunification Program allowed Sierra Leonean families to identify location of the graves of loved ones who died during the Ebola epidemic. DISCUSSION: The SLED project consolidated and utilized epidemic data recorded during the Sierra Leone Ebola Virus Disease outbreak that were collected and contributed to SLED by national and international organizations. This project has provided a foundation for developing a method of ethical and secure SLED data access while preserving the host nation's data ownership. SLED serves as a data source for the SLED Family Reunification Program and for epidemiological research. It presents an opportunity for building research capacity in Sierra Leone and provides a foundation for developing a relational database. Large outbreak data systems such as SLED provide a unique opportunity for researchers to improve responses to epidemics and indicate the need to include data management preparedness in the plans for emergency response.

The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts population-based surveillance of autism spectrum disorder (ASD) in multiple US communities among 8-year-old children. To classify ASD, ADDM sites collected text descriptions of behaviors from medical and educational evaluations which were reviewed and coded by ADDM clinicians. This process took at least four years to publish data from a given surveillance year. In 2018, we developed an alternative case definition utilizing ASD diagnoses or classifications made by community professionals. Using surveillance years 2014 and 2016 data, we compared the new and previous ASD case definitions. Compared to the prevalence based on the previous case definition, the prevalence based on the new case definition was similar for 2014 and slightly lower for 2016. Sex and race/ethnicity prevalence ratios were nearly unchanged. Compared to the previous case definition, the new case definition's sensitivity was 86% and positive predictive value was 89%. The new case definition does not require clinical review and collects about half as much data yielding more timely reporting. It also more directly measures community identification of ASD, thus allowing for more valid comparisons among communities, and reduces resource requirements while retaining similar measurement properties to the previous definition.

Long-standing systemic social, economic, and environmental inequities in the United States have put many communities of color (racial and ethnic minority groups) at increased risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, as well as more severe COVID-19-related outcomes (1-3). Because race and ethnicity are missing for a proportion of reported COVID-19 cases, counties with substantial missing information often are excluded from analyses of disparities (4). Thus, as a complement to these case-based analyses, population-based studies can help direct public health interventions. Using data from the 50 states and the District of Columbia (DC), CDC identified counties where five racial and ethnic minority groups (Hispanic or Latino [Hispanic], non-Hispanic Black or African American [Black], non-Hispanic Asian [Asian], non-Hispanic American Indian or Alaska Native [AI/AN], and non-Hispanic Native Hawaiian or other Pacific Islander [NH/PI]) might have experienced high COVID-19 impact during April 1-December 22, 2020. These counties had high 2-week COVID-19 incidences (>100 new cases per 100,000 persons in the total population) and percentages of persons in five racial and ethnic groups that were larger than the national percentages (denoted as "large"). During April 1-14, a total of 359 (11.4%) of 3,142 U.S. counties reported high COVID-19 incidence, including 28.7% of counties with large percentages of Asian persons and 27.9% of counties with large percentages of Black persons. During August 5-18, high COVID-19 incidence was reported by 2,034 (64.7%) counties, including 92.4% of counties with large percentages of Black persons and 74.5% of counties with large percentages of Hispanic persons. During December 9-22, high COVID-19 incidence was reported by 3,114 (99.1%) counties, including >95% of those with large percentages of persons in each of the five racial and ethnic minority groups. The findings of this population-based analysis complement those of case-based analyses. In jurisdictions with substantial missing race and ethnicity information, this method could be applied to smaller geographic areas, to identify communities of color that might be experiencing high potential COVID-19 impact. As areas with high rates of new infection change over time, public health efforts can be tailored to the needs of communities of color as the pandemic evolves and integrated with longer-term plans to improve health equity.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted mass drug administration (MDA) from 2000-2006. Despite passing Transmission Assessment Surveys (TAS) in 2011/2012 and 2015, American Samoa failed TAS-3 in 2016, with antigen (Ag) prevalence of 0.7% (95%CI 0.3-1.8%) in 6-7 year-olds. A 2016 community survey (Ag prevalence 6.2% (95%CI 4.4-8.5%) in age ≥8 years) confirmed resurgence. Using data from the 2016 survey, this study aims to i) investigate antibody prevalence in TAS-3 and the community survey, ii) identify risk factors associated with being seropositive for Ag and anti-filarial antibodies, and iii) compare the efficiency of different sampling strategies for identifying seropositive persons in the post-MDA setting. Antibody prevalence in TAS-3 (n = 1143) were 1.6% for Bm14 (95%CI 0.9-2.9%), 7.9% for Wb123 (95%CI 6.4-9.6%), and 20.2% for Bm33 (95%CI 16.7-24.3%); and in the community survey (n = 2507), 13.9% for Bm14 (95%CI 11.2-17.2%), 27.9% for Wb123 (95%CI 24.6-31.4%), and 47.3% for Bm33 (95%CI 42.1-52.6%). Multivariable logistic regression was used to identify risk factors for being seropositive for Ag and antibodies. Higher Ag prevalence was found in males (adjusted odds ratio [aOR] 3.01), age ≥18 years (aOR 2.18), residents of Fagali'i (aOR 15.81), and outdoor workers (aOR 2.61). Ag prevalence was 20.7% (95%CI 9.7-53.5%) in households of Ag-positive children identified in TAS-3. We used NNTestav (average number needed to test to identify one positive) to compare the efficiency of the following strategies for identifying persons who were seropositive for Ag and each antibody: i) TAS of 6-7 year-old children, ii) population representative surveys of older age groups, and iii) targeted surveillance of subpopulations at higher risk of being seropositive (older ages, householders of Ag-positive TAS children, and known hotspots). For Ag, NNTestav ranged from 142.5 for TAS, to <5 for households of index children. NNTestav was lower in older ages, and highest for Ag, followed by Bm14, Wb123 and Bm33 antibodies. We propose a multi-stage surveillance strategy, starting with population-representative sampling (e.g. TAS or population representative survey of older ages), followed by strategies that target subpopulations and/or locations with low NNTestav. This approach could potentially improve the efficiency of identifying remaining infected persons and residual hotspots. Surveillance programs should also explore the utility of antibodies as indicators of transmission.

BACKGROUND: Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-Nitroimidazoles [metronidazole (MTZ) and tinidazole (TDZ)] are FDA-approved treatments. To better understand treatment failure, we conducted a systematic review on mechanisms of 5-nitroimidazole resistance. METHODS: PubMed, ScienceDirect and EMBASE databases were searched using keywords Trichomonas vaginalis, trichomoniasis, 5-nitroimidazole, metronidazole, tinidazole and drug resistance. Non-English language articles and articles on other treatments were excluded. RESULTS: The search yielded 606 articles, of which 550 were excluded, leaving 58 articles. Trichomonas vaginalis resistance varies and is higher with MTZ (2.2-9.6%) than TDZ (0-2%). Resistance can be aerobic or anaerobic and is relative rather than absolute. Differential expression of enzymes involved in trichomonad energy production and antioxidant defenses affects 5-nitroimidazole drug activation; reduced expression of pyruvate:ferredoxin oxidoreductase, ferredoxin, nitroreductase, hydrogenase, thioredoxin reductase and flavin reductase are implicated in drug resistance. Trichomonas vaginalis infection with Mycoplasma hominis or T. vaginalis virus has also been associated with resistance. Trichomonas vaginalis has two genotypes, with greater resistance seen in type 2 (vs type 1) populations. DISCUSSION: 5-Nitroimidazole resistance results from differential expression of enzymes involved in energy production or antioxidant defenses, along with genetic mutations in the T. vaginalis genome. Alternative treatments outside of the 5-nitroimidazole class are needed.

BACKGROUND: Currently, FDA-approved HIV-1 viral load (VL) assays use venipuncture-derived plasma. The Hologic Panther system uses 0.7mL total volume for the Aptima HIV-1 Quant Assay standard (APT-Quant-std) and dilution (APT-Quant-dil) protocols. However, smaller plasma volumes from fingerstick whole blood (FSB) collected in EDTA-microtainer tubes (MCT) could provide an easier sample collection method for HIV-1 VL testing. OBJECTIVES: To evaluate the performance of the APT-Quant-std compared to the Roche CAP/CTM and Abbott m2000RT VL assays and an alternative APTQuant 1:7 dilution protocol, the latter using 100muL of MCT-derived plasma from FSB. STUDY DESIGN: Linearity was determined using commercial HIV-1 RNA plasma controls. Dilutions ranging 1.56-2.95 log10 copies/mL were prepared to determine the APT-Quant-dil Limit of Quantitation (LOQ) using Probit analysis. Specificity of APT-Quant-std was calculated using 326 HIVnegative samples. To evaluate agreement, 329 plasma specimens were tested with APT-Quant-std, CAP/CTM, and m2000RT. Forty-seven matched venipuncture and MCT-derived plasma specimens were tested with APT-Quant-std and APT-Quant-dil. RESULTS: Among the RNA controls, specificity was 99.69 % for APT-Quant-std. The R2 values were 0.988 (APT-Quant-std/CAP/CTM), 0.980 (APT-Quant-std/ m2000RT), and 0.997 (APT-Quant-std/APT-Quant-dil). The APT-Quant-dil LOQ was estimated at 2.7 log10 copies/mL (500 copies/mL) (95 %CI 2.62-2.87). At 2.3 log10 copies/mL (200 copies/mL), the overall agreement was 91.0 % for APT-Quant-std/CAP/CTM, 85.7 % for APT-Quant-std/m2000RT, and 82.9 % for APT-Quant-std/APT-Quant-dil. Quantified APT-Quant-std results were on average 0.2 log10 copies/mL higher than CAP/CTM and m2000RT and 0.14 log10 copies/mL higher than APT-Quant-dil. CONCLUSION: APT-Quant showed similar performance compared to the CAP/CTM and m2000RT assays and remains sensitive and accurate using the dilution protocol.

Purpose: Organizations responding to the 2014–2016 Ebola epidemic in Sierra Leone collected information from multiple sources and kept it in separate databases, including distinct data systems for Ebola hot line calls, patient information collected by field surveillance officers, laboratory testing results, clinical information from Ebola treatment and isolation facilities, and burial team records. Methods: After the conclusion of the epidemic, the Sierra Leone Ministry of Health and Sanitation and the U.S. Centers for Disease Control and Prevention partnered to collect these disparate records and consolidate them in the Sierra Leone Ebola Database. Results: The Sierra Leone Ebola Database data are providing a lasting resource for postepidemic data analysis and epidemiologic research, including identifying best strategies in outbreak response, and are used to help families locate the graves of family members who died during the epidemic. Conclusion: This report describes the Ministry of Health and Sanitation and Centers for Disease Control and Prevention processes to safeguard Ebola records while making the data available for public health research.

BACKGROUND: Trichomonas vaginalis virus (TVV) is a non-segmented, 4.5-5.5 kbp, double-stranded RNA virus infecting T. vaginalis. The objectives of this study were to examine TVV prevalence in U.S. Trichomonas vaginalis isolates and associations with patient demographics, clinical outcomes, and metronidazole resistance. METHODS: Archived T. vaginalis isolates from the enrollment visit of 355 women participating in a T. vaginalis treatment trial in Birmingham, AL were thawed and grown in culture. Total RNA was extracted using Trizol reagent. Contaminating single stranded RNA was precipitated using 4.0M LiCl and centrifugation. Samples were analyzed by gel electrophoresis to visualize a 4.5kbp band representative of TVV. In vitro testing for metronidazole resistance was also performed on 25/47 isolates from the test of cure visit. RESULTS: TVV was detected in 142/355 (40%) isolates at the enrollment visit. Women with TVV+ isolates were significantly older (p = 0.01), more likely to smoke (p = 0.04), and less likely to report a history of gonorrhea (p = 0.04). There was no association between the presence of clinical symptoms or repeat T. vaginalis infection with TVV+ isolates (p = 0.14 and p = 0.44, respectively). Of 25 Test of cure isolates tested for metronidazole resistance, 0/10 TVV+ isolates demonstrated resistance while 2/15 TVV- isolates demonstrated mild-moderate resistance (p = 0.23). CONCLUSIONS: In one of the largest U.S. studies of T. vaginalis isolates tested for TVV, prevalence was 40%. However, there was no association of TVV+ isolates with clinical symptoms, repeat infections, or metronidazole resistance. These results suggest that TVV may be a commensal to T. vaginalis.

The National Cancer Policy Forum of the National Academies of Sciences, Engineering and Medicine sponsored a workshop on July 24 and 25, 2017 on Long-Term Survivorship after Cancer Treatment. The workshop brought together diverse stakeholders (patients, advocates, academicians, clinicians, research funders, and policymakers) to review progress and ongoing challenges since the Institute of Medicine (IOM)'s seminal report on the subject of adult cancer survivors published in 2006. This commentary profiles the content of the meeting sessions and concludes with recommendations that stem from the workshop discussions. Although there has been progress over the past decade, many of the recommendations from the 2006 report have not been fully implemented. Obstacles related to the routine delivery of standardized physical and psychosocial care services to cancer survivors are substantial, with important gaps in care for patients and caregivers. Innovative care models for cancer survivors have emerged, and changes in accreditation requirements such as the Commission on Cancer's (CoC) requirement for survivorship care planning have put cancer survivorship on the radar. The Center for Medicare & Medicaid Innovation's Oncology Care Model (OCM), which requires psychosocial services and the creation of survivorship care plans for its beneficiary participants, has placed increased emphasis on this service. The OCM, in conjunction with the CoC requirement, is encouraging electronic health record vendors to incorporate survivorship care planning functionality into updated versions of their products. As new models of care emerge, coordination and communication among survivors and their clinicians will be required to implement patient- and community-centered strategies.

INTRODUCTION: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration (MDA) from 2000-2006. The World Health Organization recommends systematic post-MDA surveillance using Transmission Assessment Surveys (TAS) for epidemiological assessment of recent LF transmission. We compared the effectiveness of two survey designs for post-MDA surveillance: a school-based survey of children aged 6-7 years, and a community-based survey targeting people aged >/=8 years. METHODS: In 2016, we conducted a systematic school-based TAS in all elementary schools (N = 29) and a cluster survey in 28 villages on the two main islands of American Samoa. We collected information on demographics and risk factors for infection using electronic questionnaires, and recorded geo-locations of schools and households. Blood samples were collected to test for circulating filarial antigen (CFA) using the Alere Filariasis Test Strip. For those who tested positive, we prepared slides for microscopic examination of microfilaria and provided treatment. Descriptive statistics were performed for questionnaire variables. Data were weighted and adjusted to account for sampling design and sex for both surveys, and for age in the community survey. RESULTS: The school-based TAS (n = 1143) identified nine antigen-positive children and found an overall adjusted CFA prevalence of 0.7% (95% CI: 0.3-1.8). Of the nine positive children, we identified one microfilariaemic 7-year-old child. The community-based survey (n = 2507, 711 households) identified 102 antigen-positive people, and estimated an overall adjusted CFA prevalence of 6.2% (95% CI: 4.5-8.6). Adjusted village-level prevalence ranged from 0-47.1%. CFA prevalence increased with age and was higher in males. Of 86 antigen-positive community members from whom slides were prepared, 22 (25.6%) were microfilaraemic. School-based TAS had limited sensitivity (range 0-23.8%) and negative predictive value (range 25-83.3%) but had high specificity (range 83.3-100%) and positive predictive value (range 0-100%) for identifying villages with ongoing transmission. CONCLUSIONS: American Samoa failed the school-based TAS in 2016, and the community-based survey identified higher than expected numbers of antigen-positive people. School-based TAS was logistically simpler and enabled sampling of a larger proportion of the target population, but the results did not provide a good indication of the overall CFA prevalence in older age groups and was not sensitive at identifying foci of ongoing transmission. The community-based survey, although operationally more challenging, identified antigen-positive individuals of all ages, and foci of high antigen prevalence. Both surveys confirmed recrudescence of LF transmission.

HIV continuum of care analyses in Georgia during 2013 revealed that 82% of adolescents and adults living with HIV knew their diagnosis and that 75% were linked to care. However, of all persons in Georgia living with HIV in 2014, only 60% had at least one HIV care visit, and just 48% were retained in care. Understanding barriers for HIV testing, linkage, and retention in youth may strengthen HIV-related encounters and improve patient outcomes. We conducted 17 qualitative focus groups with HIV-positive and -negative youth, ages 18-24 years, from the Atlanta Metropolitan Statistical Area. Using computer-assisted thematic analyses, we examined focus group responses on ways to approach youth for community-based HIV testing and how service providers should discuss a new positive HIV diagnosis with youth. Of 68 participants, 85% were male, 90% were African American, 68% were HIV positive, and 50% had high school education or less. Mean age was 21.5 years (standard deviation: 1.8 years). Thematic analyses identified the following three key themes for approaching someone for HIV testing: (1) discretion, (2) being candid about testing, and (3) incentivizing testing. When service providers discuss an HIV positive test, participants recommended enhanced emotional support and reassurance of a potential healthy life span despite an HIV diagnosis. Community-based testing may be a viable option for increasing HIV screening of at-risk youth. Structuring an empathetic new diagnosis disclosure that addresses potential misconceptions and describes successful HIV treatment is essential to improving linkage to care among youth.

BACKGROUND: In 2000, American Samoa had 16.5% prevalence of lymphatic filariasis (LF) antigenemia. Annual mass drug administration (MDA) was conducted using single-dose albendazole plus diethylcarbamazine from 2000 to 2006. This study presents the results of a 2007 population-based PacELF C-survey in all ages and compares the adult filarial antigenemia results of this survey to those of a subsequent 2010 survey in adults with the aim of improving understanding of LF transmission after MDA. RESULTS: The 2007 C-survey used simple random sampling of households from a geolocated list. In 2007, the overall LF antigen prevalence by immunochromatographic card test (ICT) for all ages was 2.29% (95% CI 1.66-3.07). Microfilaremia prevalence was 0.27% (95% CI 0.09-0.62). Increasing age (OR 1.04 per year, 95% CI 1.02-1.05) was significantly associated with ICT positivity on multivariate analysis, while having ever taking MDA was protective (OR 0.39, 95% CI 0.16-0.96). The 2010 survey used a similar spatial sampling design. The overall adult filarial antigenemia prevalence remained relatively stable between the surveys at 3.32% (95% CI 2.44-4.51) by ICT in 2007 and 3.23 (95% CI 2.21-4.69) by Og4C3 antigen in 2010. However, there were changes in village-level prevalence. Eight village/village groupings had antigen-positive individuals identified in 2007 but not in 2010, while three villages/village groupings that had no antigen-positive individuals identified in 2007 had positive individuals identified in 2010. CONCLUSIONS: After 7 years of MDA, with four rounds achieving effective coverage, a representative household survey in 2007 showed a decline in prevalence from 16.5 to 2.3% in all ages. However, lack of further decline in adult prevalence by 2010 and fluctuation at the village level showed that overall antigenemia prevalence at a broader scale may not provide an accurate reflection of ongoing transmission at the village level.

OBJECTIVE: To determine the effectiveness of the Metropolitan Atlanta community adolescent rapid testing initiative (MACARTI) intervention relative to standard of care (SOC), in achieving early diagnosis, linkage, and retention among HIV-infected youth ages 18-24 years. DESIGN: MACARTI was a pilot single-center, prospective, nonrandomized study. METHODS: MACARTI combined nontraditional venue HIV testing, motivational interviewing, and case management. We collected demographic, clinical variables and calculated linkage and appointment adherence rates. We obtained SOC data from an adolescent HIV clinic. Longitudinal data were analyzed using inverse propensity treatment-weighted linear growth models; medians, interquartile ranges (IQR), means, and 95% confidence intervals are provided. RESULTS: MACARTI screened 435 participants and identified 49 (11.3%) HIV infections. The SOC arm enrolled 49 new HIV-infected individuals. The 98 participants, (49 in each arm) were: 85% men; 91% Black; mean age = 21 years (SD : 1.8). Overall, 63% were linked within 3 months of diagnosis; linkage was higher for MACARTI compared to SOC (96 vs. 57%, P < 0.001). Median linkage time for MACARTI participants compared to SOC was 0.39 (IQR : 0.20-0.72) vs. 1.77 (IQR : 1.12-12.65) months (P < 0.001). MACARTI appointment adherence was higher than SOC (86.1 vs. 77.2%, P = 0.018). In weight-adjusted models, mean CD4 T-cell counts increased and mean HIV-1 RNA levels decreased in both arms over 12 months, but the differences were more pronounced in the MACARTI arm. CONCLUSION: MACARTI successfully identified and linked HIV-infected youth in Atlanta, USA. MACARTI may serve as an effective linkage and care model for clinics serving HIV-infected youth.

Francisella tularensis (Ft) is a highly virulent zoonotic pathogen that causes tularemia, and because of weaponization efforts in past world wars, is considered a Tier 1 biothreat agent. Detection and surveillance of Ft may be confounded by the presence of uncharacterized, closely related organisms. Through DNA-based diagnostics and environmental surveys, novel clinical and environmental Francisella isolates have been obtained in recent years. Here we present 17 new Francisella genomes and a comparison of their characteristics to each other and to 14 publicly available genomes as well as a comparative analysis of 16S rRNA and sdhA genes from over 90 Francisella strains. Delineation of new species in bacteria is challenging, especially when isolates having very close genomic characteristics exhibit different physiological features - for example, when some are virulent pathogens in humans and animals, while others are non-pathogenic or are opportunistic pathogens. Species resolution within Francisella varies with analyses of single genes, multiple gene or protein sets, or whole genome comparisons of nucleic acid and amino acid sequences. Analyses focusing on single genes (16S rRNA, sdhA), multiple gene sets (virulence genes, LPS biosynthesis, pathogenicity island) and whole genome comparisons (nucleotide and protein) gave congruent results, but with different discrimination confidence. We designate four new species within the genus; Francisella opportunistica sp. nov. (MA06-7296), Francisella salina sp. nov. (TX07-7308), Francisella uliginis sp. nov. (TX07-7310), and Francisella frigiditurris sp. nov. (CA97-1460). This study provides a robust comparative framework to discern species and virulence features of newly detected Francisellas IMPORTANCE: DNA-based detection and sequencing methods have identified thousands of new bacteria in the human body and the environment. In most cases, there are no cultured isolates that correspond to these sequences. While DNA-based approaches are highly sensitive, accurately assigning species is difficult without known near-relatives for comparison. This ambiguity poses challenges for clinical cases, disease epidemics and environmental surveillance, where response times must be short. Many new Francisella isolates have been identified globally. However, their species designations and potential for causing human disease remain ambiguous. Through detailed genome comparisons, we identified features that differentiate F. tularensis from clinical and environmental Francisella isolates and provide a knowledge base for future comparison of Francisellas identified in clinical samples or environmental surveys.

The Global Programme to Eliminate Lymphatic Filariasis has made significant progress toward interrupting transmission of lymphatic filariasis (LF) through mass drug administration (MDA). Operational challenges in defining endpoints of elimination programs include the need to determine appropriate post-MDA surveillance strategies. As humans are the only reservoirs of LF parasites, one such strategy is molecular xenomonitoring (MX), the detection of filarial DNA in mosquitoes using molecular methods (PCR), to provide an indirect indicator of infected persons nearby. MX could potentially be used to evaluate program success, provide support for decisions to stop MDA, and conduct post-MDA surveillance. American Samoa has successfully completed MDA and passed WHO recommended Transmission Assessment Surveys in 2011 and 2015, but recent studies using spatial analysis of antigen (Ag) and antibody (Ab) prevalence in adults (aged ≥18 years) and entomological surveys showed evidence of possible ongoing transmission. This study evaluated MX as a surveillance tool in American Samoa by linking village-level results of published human and mosquito studies. Of 32 villages, seropositive persons for Og4C3 Ag were identified in 11 (34.4%), for Wb123 Ab in 18 (56.3%) and for Bm14 Ab in 27 (84.4%) of villages. Village-level seroprevalence ranged from 0-33%, 0-67% and 0-100% for Og4C3 Ag, Wb123 Ab and Bm14 Ab respectively. PCR-positive Aedes polynesiensis mosquitoes were found in 15 (47%) villages, and their presence was significantly associated with seropositive persons for Og4C3 Ag (67% vs 6%, p<0.001) and Wb123 Ab (87% vs 29%, p = 0.001), but not Bm14 Ab. In villages with persons seropositive for Og4C3 Ag and Wb123 Ab, PCR-positive Ae. polynesiensis were found in 90.9% and 72.2% respectively. In villages without seropositive persons for Og4C3 Ag or Wb123 Ab, PCR-positive Ae. polynesiensis were also absent in 94.1% and 70.6% of villages respectively. Our study provides promising evidence to support the potential usefulness of MX in post-MDA surveillance in an Aedes transmission area in the Pacific Islands setting.