BACKGROUND: Limited data are available regarding the development and durability of immune responses following COVID-19 infection or vaccination in pediatric solid-organ transplant (SOT) recipients. METHODS: Renal, liver, or intestinal transplant recipients < 21 years of age followed at Seattle Children's Hospital were enrolled from August 2020 to May 2021. Blood samples were collected at ~6-month intervals for up to 3 years and tested for antinucleocapsid (N) antibodies. COVID-19 vaccination data were collected from the Washington State Immunization Information System and/or the medical record. Semi-quantitative anti-S IgG testing was performed on all postvaccine samples using the Abbott Architect platform. We further evaluated a subset of postvaccine samples using variant-specific quantitative binding (Meso Scale Discovery, MSD) immunoassays and pseudovirus-neutralization assays. Antibody levels were compared over time and by vaccine category. RESULTS: We followed 83 SOT recipients for a median of 12.5 months (IQR 7.0, 28.3). Overall, 16 (19.3%) participants had evidence of SARS-CoV-2 infection based on anti-N antibody detection. Forty-six (55%) participants had a blood sample collected > 14 days after receipt of a vaccination. Serum IgG to spike antigens (anti-S antibody) increased following vaccination and increased with the number of vaccine doses received as assessed by both the Abbott and MSD assays. Neutralizing activity was significantly lower against the Omicron subvariants compared to the ancestral strain. CONCLUSION: Pediatric SOT recipients demonstrated strong antibody responses following SARS-CoV-2 vaccination, with higher anti-S antibody responses following > 2 doses of vaccine. Our study offers unique longitudinal immune response data in this vulnerable patient population.

BACKGROUND: Uzbekistan, a highly endemic country for hepatitis B virus (HBV), introduced infant vaccination with hepatitis B vaccine (HepB) in 2001. Since 2002, it had ≥90 % reported immunization coverage for ≥3 doses of HepB (HepB3) and the birth dose (HepB-BD). However, the impact of HepB vaccination and the progress towards achieving the regional hepatitis B control and global viral hepatitis B elimination goals had not been assessed. METHODS: To determine current HBsAg prevalence among children in Uzbekistan, in 2022, we conducted a nationwide serosurvey among schoolchildren (grades 1-3) using a stratified, multi-stage cluster design. Participants' basic demographics and HepB immunization information were obtained. Blood specimens were tested for HBsAg using a WHO-prequalified rapid test (Bioline HBsAg WB, Abbott Diagnostics). Samples with positive and indeterminate results were tested for HBsAg by ELISA (Murex HBsAg Version3, Diasorine). Weighted proportions and adjusted 95 % confidence intervals (CI) were calculated. RESULTS: Of 4119 children enrolled in 148 schools, blood was collected from 3753 (91.1 %) and immunization data were available for 3833 (93.3 %). National HBsAg prevalence was 0.20 % (adjusted 95 % CI, 0.09 %-0.38 %). Among children with available immunization data, 97.7 % (97.2 %-98.1 %) received ≥3 HepB doses and 94.9 % (94.1 %-95.5 %) received HepB-BD, including timely HepB-BD in 93.7 % (92.9 %-94.5 %). CONCLUSIONS: The survey demonstrated that Uzbekistan has met the <0.5 % European regional HBsAg seroprevalence target and has made substantial progress towards meeting the <0.1 % HBsAg seroprevalence target for the elimination of HBV mother to-child transmission (MTCT). Based on these findings and ≥ 90 % HepB-BD and HepB3 coverage, in 2023, Uzbekistan was validated as having achieved the regional hepatitis B control goal. To achieve the elimination of MTCT of HBV, additional interventions, including improving antenatal screening for HBsAg, providing antiviral treatment of eligible HBsAg-positive pregnant women and hepatitis B immunoglobulin to infants born to HBsAg-positive mothers, should be considered.

Epidemiological delays are key quantities that inform public health policy and clinical practice. They are used as inputs for mathematical and statistical models, which in turn can guide control strategies. In recent work, we found that censoring, right truncation, and dynamical bias were rarely addressed correctly when estimating delays and that these biases were large enough to have knock-on impacts across a large number of use cases. Here, we formulate a checklist of best practices for estimating and reporting epidemiological delays. We also provide a flowchart to guide practitioners based on their data. Our examples are focused on the incubation period and serial interval due to their importance in outbreak response and modeling, but our recommendations are applicable to other delays. The recommendations, which are based on the literature and our experience estimating epidemiological delay distributions during outbreak responses, can help improve the robustness and utility of reported estimates and provide guidance for the evaluation of estimates for downstream use in transmission models or other analyses.

OBJECTIVES: CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. METHODS: CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020-2021) and KEQAS (2020-2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). RESULTS: Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from -29.28 to 9.86 %, into -0.09-0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from -23.78 to 2.00 % pre-harmonization to -3.13-1.42 % post-harmonization. CONCLUSIONS: The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Congenital transmission of Toxoplasma gondii can occur when a woman becomes infected for the first time during or just before pregnancy. Toxoplasma gondii in the fetus can lead to miscarriage, stillbirth, ocular or neurological abnormalities at birth, or progressive visual, hearing, motor, and cognitive deficiencies. The national seroprevalence of T. gondii infection in Nigeria was previously unknown. The 2018 Nigeria HIV/AIDS Indicator and Impact Survey collected demographic, socioeconomic, and HIV-related data and stored blood specimens with consent for future analysis for other pathogens of public health importance. We evaluated toxoplasmosis seropositivity and risk factors in a sample of 44,269 women of reproductive age (WRA) between 15 and 44 years. The national T. gondii seroprevalence among WRA was 26.8% (95% CI: 25.8-27.7%). We found that WRA from all 36 states and the Federal Capital Territory had T. gondii exposure. Seroprevalence was higher in 25- to 44-year-olds than in 15- to 24-year-olds. A similar proportion of pregnant and nonpregnant women were seropositive. Increased odds of seropositivity were associated with unimproved toilet facilities and drinking water sources, being in a higher wealth quintile, and primary and secondary education compared with no education. Decreased odds of seropositivity were associated with living in an urban area and owning livestock. This study provides the first-ever national seroprevalence estimate for WRA in Nigeria. Although information on known risk factors for toxoplasmosis (e.g., consumption of undercooked meat, cat ownership) was not collected, future studies could further investigate potential risk factors to inform the development of effective toxoplasmosis prevention measures.

BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants.

BACKGROUND: Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. METHODS: From October to December 2020, we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon's 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbott Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. RESULTS: The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%-9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case being reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. CONCLUSION: This study's findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon-an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

INTRODUCTION: Highly sensitive acute flaccid paralysis (AFP) surveillance is critical for detection of poliovirus circulation and documentation for polio-free certification. The reverse cold chain (RCC) is a system designed to maintain stool specimens in appropriate temperature for effective detection of poliovirus in the laboratory. We monitored the RCC of AFP surveillance in Nigeria to determine its effectiveness in maintaining viability of enterovirus. METHODS: A descriptive cross-sectional study was conducted from November 2017 to December 2019. We included AFP cases from 151 Local Government Areas and monitored RCC of paired stool specimens from collection to arrival at laboratories. The national guideline recommends RCC temperature of +2 to +8°C and a non-polio enterovirus (NPENT) detection rate of ≥10%. We analyzed data with Epi Info 7, and presented results as frequencies and proportions, using Chi-square statistic to test for difference in enterovirus isolation. RESULTS: Of the 1,042 tracked paired stool specimens, 1,038(99.6%) arrived at the laboratory within 72 hours of collection of second specimen, 824(79.1%) were maintained within recommended temperature range, and 271(26%) yielded enteroviruses: 200(73.8%) NPENT, 66(24.4%) Sabin, 3(1.1%) vaccine derived poliovirus type 2 and 2(0.7%) mixture of Sabin and NPENT. The NPENT and Sabin rates were 19.2% and 6.7% respectively. Twenty-five percent of 824 specimens maintained within recommended temperature range, compared with 29.8% of 218 specimens with temperature excursion yielded enteroviruses (P=0.175). CONCLUSION: the RCC of AFP surveillance system in the study area was optimal and effective in maintaining the viability of enteroviruses. It was unlikely that poliovirus transmission was missed during the intervention.

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

BACKGROUND: Sexually transmitted infections (STIs) such as syphilis and HIV remain to be a significant public health issue worldwide. Dual rapid point-of-care tests (POCTs) have shown promise for detecting antibodies to HIV and syphilis but have not been fully evaluated in the field. Our study supported the WHO ProSPeRo study on Sexually Transmitted Infection Point-of-Care Testing (STI POCT) by providing external quality assessment (EQA) for HIV and syphilis testing in reference laboratories and their associated clinical sites in seven countries. METHODS: HIV/syphilis serum liquid and dried tube specimen (DTS) panels were prepared by CDC. Liquid panels were distributed to the reference laboratories for three rounds of testing using commercially and locally available laboratory-based serological tests. DTS panels were sent to the clinical testing sites for 8 rounds of POC testing using the Abbott SD BIOLINE HIV/Syphilis Duo test (hereafter referred to as SD BIOLINE) and the Chembio Dual Path Platform (DPP) HIV-Syphilis assay. EQA panels were tested at CDC using the Rapid Plasma Reagin (RPR) test and the Treponema pallidum Particle Agglutination assay (TP-PA) for syphilis antibodies. Genetic Systems HIV-1/HIV-2 Plus O EIA, Geenius HIV Supplemental Assay and the Oraquick Advance HIV test were used to detect HIV antibodies in the EQA panels. Results from the reference laboratories and POCT sites were compared to those obtained at the CDC and a percentage agreement was calculated. RESULTS: Qualitative RPR and TP-PA performed at the reference laboratories demonstrated 95.4-100% agreement with CDC results while quantitative RPR and TP-PA tests demonstrated 87.7% and 89.2% agreement, respectively. A 93.8% concordance rate was observed for qualitative HIV testing in laboratories. EQA testing at clinical sites using dual tests showed 98.7% and 99.1% agreement for detection of HIV antibodies and eight out of 10 sites had > 95.8% agreement for syphilis testing. However, two clinical sites showed only 65.0-66.7% agreement for SD BIOLINE and 84.0-86.7% for DPP, respectively, for syphilis testing. CONCLUSIONS: Overall, laboratories demonstrated high EQA performance in this study. Both HIV/syphilis POCTs gave expected results in the clinic-based evaluations using DTS. However, testing errors were identified in a few testing sites suggesting the necessity for continuous training and monitoring the quality of POC testing.

INTRODUCTION: following the spread of the COVID-19 pandemic to Nigeria, the Federal Government of Nigeria restricted human and vehicular movements to curb the spread of the disease. This action had a negative impact on Acute Flaccid Paralysis (AFP) surveillance, with a resultant reduction in the number of AFP cases reported. This paper describes the impact of the COVID-19 pandemic on poliovirus surveillance in Nigeria and the proactive interventions by Nigeria´s polio program to mitigate the impact of COVID-19 on polio surveillance. METHODS: nine innovative strategies were implemented in all 774 Local Government Areas (LGA) of the 36 states and Federal Capital Territory (FCT) of the country. These strategies were developed by the national surveillance officers and operationalized by sub-national surveillance officers with different strategies starting at different epidemiological weeks from week 14 to 23, 2020. Many of the strategy innovations were technology-based and included: the use of mobile phones to send the AFP case definition and video by WhatsApp or by SMS, the use of state-specific toll-free numbers and Mobile Telephone Network (MTN) (mobile service provider) CallerfeelTM to community informants (CI) who were the main targets of the interventions to increase case detection and reporting. Others included the use of abridged e-surveillance integrated supportive supervision (ISS) checklists, virtual monthly DSNO meetings, and batched AFP stool specimen transportation network. RESULTS: compared to the same period in 2019, the cumulative rate of AFP case detection and reporting had gradually declined from 39.1% in January to 16.7% before the commencement of the interventions in week 20, 2020. However, the detection and reporting increased by 57.% from week 20 to week 47 compared to the same period in 2019. This is because with COVID-19, hospital visitation dropped, and the sick remained in the communities, so the CI network was relied on to detect and report AFP cases. The cumulative proportion of AFP cases reported by community informants as of week 47 increased from 13% in 2018 to 21% in 2020. This indicates an increase of 38%. Thirty-five AFP cases were detected and reported using the MTN Caller Feel strategy, while 15 cases were reported through state-specific toll-free numbers. CONCLUSION: the implementation of the innovative strategies was able to mitigate the low AFP case detection and reporting observed at the initial stage of the COVID-19 pandemic. The use of technology facilitated reaching the CI network, which was more instrumental in detecting and reporting the cases.

INTRODUCTION: acute flaccid paralysis (AFP) surveillance is the gold standard of the Global Polio Eradication Initiative (GPEI) for detecting cases of poliomyelitis and tracking poliovirus transmission. Nigeria's AFP surveillance performance indicators are among the highest in countries of the World Health Organization (WHO) African Region. The primary AFP surveillance performance indicators are the rate of non-polio AFP among children and the proportion of timely, adequate specimen collection. The surveillance working group of the National Emergency Operations Centre assessed the quality of AFP surveillance data in some reportedly high-performing states. METHODS: we conducted a retrospective review of AFP surveillance performance indicators in Nigeria for 2010-2019. We also reviewed data in reports from four groups of surveillance peer reviews and validation visits (conducted by in-country GPEI partners) during August 2017-May 2019 in 16 states with high primary AFP surveillance indicators; the validation visits reviewed clinical information and the dates of specimen collection and onset of paralysis with caretakers. RESULTS: there were consistently increasing AFP surveillance primary performance indicators during 2010-2016, followed by declines during 2017-2019. From the data for 16 states with peer reviews conducted from August 2017-May 2019, overall concordance of reported and "true" (validated) AFP indicator data in peer review investigations was highly variable. True AFP concordance ranged from 58%-100%, and stool timeliness concordance ranged from 56%-95%. The most common clinical causes of reported AFP cases that were not true AFP were spastic paralysis, malaria, sickle cell disease, and malnutrition. All the states that participated in peer reviews developed surveillance improvement plans based on the gaps identified. CONCLUSION: Nigeria has highly sensitive AFP surveillance according to reported primary AFP performance indicators. The findings of peer reviews indicate that the AFP surveillance system needs to be strengthened and well-supervised to enhance data quality.

INTRODUCTION: novel oral poliovirus vaccine type 2 (nOPV2), designed to be more genetically stable than Sabin-strain oral poliovirus vaccine type 2 (mOPV2), is a new and key component of the Global Polio Eradication Initiative's strategy to combat outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2). The World Health Organization´s (WHO´s) emergency use listing (EUL) requires extensive safety monitoring for Adverse Event of Special Interest (AESI) in its use. We implemented AESI active surveillance to monitor the safety of the nOPV2 in Nigeria. METHODS: a cross-sectional assessment was conducted in Nigeria during March-June 2021 in 117 local government areas (LGAs) across 6 states and the Federal Capital Area with confirmed cVDPV2 transmission. We conducted active searches for nOPV2 AESI in all health facilities. Suspected events were ascertained, and vaccination and clinical data abstracted. Events were classified using WHO causality assessment algorithm. Data were analyzed using Epi info7. RESULTS: total of 234 adverse events were reported after 21,997,300 doses of nOPV2 were administered, giving a crude reported incidence of 1 in 94,000 doses of nOPV2. Altogether, 221 of the 234 (94%) adverse events were classified. For 166 AESI ascertained to occur following a dose of nOPV2, the corrected crude incidence rate was 1 in 133,000 doses; 4 of the adverse events, were classified as consistent with casual association with nOPV2 vaccination. CONCLUSION: we found that nOPV2 had a low incidence of AESI following nOPV2 campaigns and no new or unexpected adverse event was reported. Safety monitoring should be sustained for early detection of signals and uncommon adverse events.

Background Rapid diagnostic tests (RDTs) for SARS-CoV-2 antigens (Ag) that can be performed at point-of-care (POC) can supplement molecular testing and help mitigate the COVID-19 pandemic. Deployment of an Ag RDT requires an understanding of its operational and performance characteristics under real-world conditions and in relevant subpopulations. We evaluated the Abbott BinaxNOW™ COVID-19 Ag Card in a high-throughput, drive-through, free community testing site in Massachusetts (MA) using anterior nasal (AN) swab RT-PCR for clinical testing.Methods Individuals presenting for molecular testing in two of seven lanes were offered the opportunity to also receive BinaxNOW testing. Dual AN swabs were collected from symptomatic and asymptomatic children (≤ 18 years) and adults. BinaxNOW testing was performed in a testing pod with temperature/humidity monitoring. One individual performed testing and official result reporting for each test, but most tests had a second independent reading to assess inter-operator agreement. Positive BinaxNOW results were scored as faint, medium, or strong. Positive BinaxNOW results were reported to patients by phone and they were instructed to isolate pending RT-PCR results. The paired RT-PCR result was the reference for sensitivity and specificity calculations.Results Of 2482 participants, 1380 adults and 928 children had paired RT-PCR/BinaxNOW results and complete symptom data. 974/1380 (71%) adults and 829/928 (89%) children were asymptomatic. BinaxNOW had 96.5% (95% confidence interval [CI] 90.0-99.3) sensitivity and 100% (98.6-100.0) specificity in adults within 7 days of symptoms, and 84.6% (65.1-95.6) sensitivity and 100% (94.5-100.0) specificity in children within 7 days of symptoms. Sensitivity and specificity in asymptomatic adults were 70.2% (56.6-81.6) and 99.6% (98.9-99.9), respectively, and in asymptomatic children were 65.4% (55.6-74.4) and 99.0% (98.0-99.6), respectively. By cycle threshold (Ct) value cutoff, sensitivity in all subgroups combined (n=292 RT-PCR-positive individuals) was 99.3% with Ct ≤25, 95.8% with ≤30, and 81.2% with ≤35. Twelve false positive BinaxNOW results (out of 2308 tests) were observed; in all twelve, the test bands were faint but otherwise normal, and were noted by both readers. One invalid BinaxNOW result was identified. Inter-operator agreement (positive versus negative BinaxNOW result) was 100% (n = 2230/2230 double reads). Each operator was able to process 20 RDTs per hour. In a separate set of 30 specimens (from individuals with symptoms ≤7 days) run at temperatures below the manufacturer’s recommended range (46-58.5°F), sensitivity was 66.7% and specificity 95.2%.Conclusions BinaxNOW had very high specificity in both adults and children and very high sensitivity in newly symptomatic adults. Overall, 95.8% sensitivity was observed with Ct ≤ 30. These data support public health recommendations for use of the BinaxNOW test in adults with symptoms for ≤7 days without RT-PCR confirmation. Excellent inter-operator agreement indicates that an individual can perform and read the BinaxNOW test alone. A skilled laboratorian can perform and read 20 tests per hour. Careful attention to temperature is critical.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was funded by the MA Department of Public Health. The community testing site was funded by the Centers for Disease Control and Prevention Building and Enhancing Epidemiology, Laboratory and Health Information Systems Capacity in Massachusetts--Enhancing Detection COVID Supplement (Grant # 6 NU50CK000518-01-08). BinaxNOW kits were supplied as part of the federal allocation to state health departments.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was reviewed by the Massachusetts Department of Public Health IRB and deemed not human subject research.All 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.YesAll data referred to in the manuscript are publicly available.

Trachoma is an infectious disease characterized by repeated exposures to Chlamydia trachomatis (Ct) that may ultimately lead to blindness. Certain areas, particularly in Africa, pose persistent challenges to elimination of trachoma as a public health problem. Efficiently identifying communities with high infection burden could help target more intensive control efforts. We hypothesized that IgG seroprevalence in combination with geospatial layers, machine learning, and model-based geostatistics would be able to accurately predict future community-level ocular Ct infections detected by PCR. We used measurements from 40 communities in the hyperendemic Amhara region of Ethiopia. Median Ct infection prevalence among children 0-5 years old increased from 6% at enrollment to 29% by month 36. At baseline, correlation between seroprevalence and Ct infection was stronger among children 0-5 years old (ρ = 0.77) than children 6-9 years old (ρ = 0.48), and stronger than the correlation between clinical trachoma and Ct infection (0-5y ρ = 0.56; 6-9y ρ = 0.40). Seroprevalence was the strongest concurrent predictor of infection prevalence at month 36 among children 0-5 years old (cross-validated R2 = 0.75, 95% CI: 0.58-0.85), though predictive performance declined substantially with increasing temporal lag between predictor and outcome measurements. Geospatial variables, a spatial Gaussian process, and stacked ensemble machine learning did not meaningfully improve predictions. Serological markers among children 0-5 years old may be an objective, programmatic tool for identifying communities with high levels of active ocular Ct infections, but accurate, future prediction in the context of changing transmission remains an open challenge.SIGNIFICANCE STATEMENT Trachoma is targeted for elimination as a public health problem by 2030. District-level estimates of clinical disease among children 1-9 years old are currently used to guide control programs and assess elimination. However, clinical trachoma is a subjective indicator. Serological markers present an objective, scalable alternative that could be measured in integrated platforms. In a hyperendemic region, community-level seroprevalence aligned more closely with concurrent infection prevalence than clinical trachoma. The correlation between seroprevalence and infection prevalence was stronger among 0–5-year-olds compared to 6–9-year-olds and was consistent over a three-year period of increasing transmission. Serosurveillance among children 0-5 years old may be a promising monitoring strategy to identify communities with the highest burdens of ocular chlamydial infection.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialNCT02754583Funding StatementWe would like to thank the WUHA study participants and field team without whom this research would not be possible. This work was supported by the National Institute of Allergy and Infectious Diseases (R03 AI147128 to BFA) and the National Eye Institute (U10 EY023939 to JDK). This work was also made possible in part by an Unrestricted Grant from Research to Prevent Blindness. We would also like to thank Abbott for its donation of the m2000 RealTime molecular diagnostics system and consumables.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study was obtained from the University of California, San Francisco Institutional Review Board (14-14004).All 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.YesDe-identified data and code to replicate this work is available on Github. https://github.com/ctedijanto/swift-spatial-prediction

Malaria diagnostic testing in Africa is threatened by Plasmodium falciparum parasites lacking histidine-rich protein 2 (pfhrp2) and 3 (pfhrp3) genes. Among 12,572 subjects enrolled along Ethiopia’s borders with Eritrea, Sudan, and South Sudan and using multiple assays, we estimate HRP2-based rapid diagnostic tests would miss 9.7% (95% CI 8.5-11.1) of falciparum malaria cases due to pfhrp2 deletion. Established and novel genomic tools reveal distinct subtelomeric deletion patterns, well-established pfhrp3 deletions, and recent expansion of pfhrp2 deletion. Current diagnostic strategies need to be urgently reconsidered in Ethiopia, and expanded surveillance is needed throughout the Horn of Africa.Competing Interest StatementJBP reports research support from Gilead Sciences, honoraria from Virology Education for medical education teaching, and non-financial support from Abbott Diagnostics, all outside the scope of the current work. SMF reports research support from AccessBio, outside of the current work.Funding StatementThis work was funded by the Global Fund to Fight AIDS, Tuberculosis, and Malaria through the Ministry of Health-Ethiopia (EPHI5405 to SMF) and the World Health Organization (JAC, JBP). It was also partially supported by MSF Holland, which supported field work in Gambella Region, the Doris Duke Charitable Foundation (JBP), and the US National Institutes of Health (R01AI132547 to JJJ, JAB, OA, and JBP; K24AI134990 to JJJ).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethical approval was obtained from the Ethiopia Public Health Institute (EPHI) Institutional Review Board (IRB; protocol EPHI-IRB-033-2017) and WHO Research Ethics Review Committee (protocol: ERC.0003174 001). Processing of de-identified samples and data at UNC was determined to constitute non-human subjects research by the UNC IRB (study 17-0155). The study was determined to be non-research by the Centers for Disease Control and Prevention Human Subjects office (0900f3eb81bb60b9).All 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.YesGenomic sequencing data will be available through the Sequence Read Archive (BioSample accession numbers pending). De-identified datasets generated during the current study will be available as supplementary files. Code used during data analysis will be made available on GitHub.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information&amp; Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. &amp; Charlene Zalesky, and Claudia &amp; Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill &amp; Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, &amp; Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll 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.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44

Background Given the challenges and costs associated with implementing HIV-1 incidence assay testing, there is great interest in evaluating the use of commercial HIV diagnostic tests for determining recent HIV infection. A diagnostic test with the capability of providing reliable data for the determination of recent HIV infection without substantial modifications to the test protocol would have a significant impact on HIV surveillance. The Abbott ARCHITECT HIV Ag/Ab Combo Assay is an antigen/antibody immunoassay, which meets the criteria as the first screening test in the recommended HIV laboratory diagnostic algorithm for the United States.Methods In this study, we evaluated the performance characteristics of the ARCHITECT HIV Ag/Ab Combo signal-to-cutoff ratio (S/Co) for determining recent infection, including estimation of the mean duration of recent infection (MDRI) and false recent rate (FRR), and selection of recency cutoffs.Results The MDRI estimates for the S/Co recency cutoff of 400 is within the 4 to 12 months range recommended for HIV incidence assays, and the FRR rate for this cutoff was 1.5%. Additionally, ARCHITECT Combo S/Co values were compared relative to diagnostic test results from two prior prospective HIV-1 diagnostic studies in order to validate the use of the S/Co for both diagnostic and recency determination.Conclusion Dual-use of the ARCHITECT Combo assay data for diagnostic and incidence purposes would reduce the need for separate HIV incidence testing and allow for monitoring of recent infection for incidence estimation and other public health applications.

Importance: Antenatal care provides unique opportunities to assess SARS-CoV-2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. Objective(s): Estimate seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid (anti-N) IgG) among pregnant people, and evaluate transplacental transfer efficiency. Design(s): Seroprevalence study: cross-sectional SARS-CoV-2 antibody screening among pregnant people December 9, 2020-June 19, 2021. Cohort study: Pregnant people screened anti-N IgG+ by Abbott Architect chemiluminescent immunoassay in seroprevalence study or identified through medical records with RT-PCR+ or antigen positive results enrolled in a prospective cohort December 9, 2020-June 30, 2022 to longitudinally measure anti-N IgG responses. We collected cord blood and assessed transplacental transfer of maternally-derived anti-N antibodies. Setting(s): Three hospitals and 14 affiliated clinics providing antenatal and delivery care, Seattle, Washington metropolitan area. Participant(s): Seroprevalence study: pregnant people were screened for SAR-CoV-2 anti-N IgG during routine care. Cohort study: Pregnant people with evidence of prior SARS-CoV-2 infection (screened anti-N IgG+ from seroprevalence study or identified with a RT-PCR+ or antigen positive result from medical records) were enrolled in a cohort study to longitudinally measure anti-N IgG responses. Exposure(s) (for observational studies): COVID-19 diagnosis, symptoms, and disease severity. Main Outcome(s) and Measure(s): Presence and durability of SARS-CoV-2 anti-N IgG, transplacental transfer of maternally-derived anti-N IgG. Result(s): Of 1289 pregnant people screened in the seroprevalence study, 5% (65) tested SARS-CoV-2 anti-N IgG+, including 39 (60%) without prior RT-PCR+ or antigen positive results and 53 (82%) without symptoms. Among 89 participants enrolled in the cohort study, 73 (82%) had anti-N IgG+ results during pregnancy. Among 49 participants with delivery samples 33 (67%) were anti-N IgG negative by delivery. Of 24 remaining anti-N IgG+ at delivery with paired cord blood samples, 12 (50%) had efficient transplacental anti-N IgG antibody transfer. Median time from first anti-N IgG to below positive antibody threshold was 17 weeks and did not differ by prior RT-PCR+ or antigen positive status. Conclusions and Relevance: Maternally-derived SARS-CoV-2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants. 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.

Point-of-care antigen tests are an important tool for SARS-CoV-2 detection, but they are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this study was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.52 for antigen testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and we have made our code publicly available to aid public health practitioners in developing or fine-tuning their own screening rules. 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.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a position statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the task force used an iterative process and expert consensus to finalize the position statement. The objective of this position statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm(3) (interquartile range [IQR], 307 to 654) and 811 cells/mm(3) (IQR, 647 to 1,013), respectively (P < 0.0001). Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm(3)) than those with undetectable ARVs (385.5 cells/mm(3)). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm(3), and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs. We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm(3)) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Reconstructing the incidence of SARS-CoV-2 infection is central to understanding the state of the pandemic. Seroprevalence studies are often used to assess cumulative infections as they can identify asymptomatic infection. Since July 2020, commercial laboratories have conducted nationwide serosurveys for the U.S. CDC. They employed three assays, with different sensitivities and specificities, potentially introducing biases in seroprevalence estimates. Using models, we show that accounting for assays explains some of the observed state-to-state variation in seroprevalence, and when integrating case and death surveillance data, we show that when using the Abbott assay, estimates of proportions infected can differ substantially from seroprevalence estimates. We also found that states with higher proportions infected (before or after vaccination) had lower vaccination coverages, a pattern corroborated using a separate dataset. Finally, to understand vaccination rates relative to the increase in cases, we estimated the proportions of the population that received a vaccine prior to infection.

Point-of-care antigen tests are an important tool for SARS-CoV-2 detection yet are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this analysis was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.53 for antigen testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and our code is publicly available to aid public health practitioners in developing or fine-tuning their own case definitions.

SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

BACKGROUND: To improve understanding of the antibody response to SARS-CoV-2 infection, we examined seroprevalence, incidence of infection, and seroconversion among a cohort of young adults living on university campuses during the fall of 2020. METHODS: At the beginning (semester start) and end (semester end) of an 11-week period, serum collected from 107 students was tested using the qualitative Abbott Architect SARS-CoV-2 IgG and AdviseDx SARS-CoV-2 IgG II assays. Results were matched to interim weekly surveillance viral testing and symptom data. RESULTS: With the SARS-CoV-2 IgG assay, 15 (14.0%) students were seropositive at semester start; 29 (27.1%) students were seropositive at semester end; 10 (9.3%) were seropositive at both times. With the AdviseDx SARS-CoV-2 IgG II assay, 17 (16.3%) students were seropositive at semester start, 37 (35.6%) were seropositive at semester end, and 16 (15.3%) were seropositive at both times. Overall, 23 students (21.5%) had positive viral tests during the semester. Infection was identified by serial testing in a large majority of individuals who seroconverted using both assays. Those seropositive at semester end more frequently reported symptomatic infections (56.5%) than asymptomatic infections (30.4%). CONCLUSION: Differences between antibody targets were observed, with more declines in antibody index values below the threshold of positivity with the anti-nucleocapsid assay compared to the anti-spike assay. Serology testing, combined with serial viral testing, can detect seroconversions, and help understand the potential correlates of protection provided by antibodies to SARS-CoV-2.

Chagas disease, or American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. Chagas disease is endemic in rural areas of Latin America, but T. cruzi, triatomine vectors, infected mammalian reservoir hosts, and rare cases of autochthonous vector borne transmission have been reported in the United States (1). Possible modes of transmission include the following: vector borne via skin or mucosal contact with feces of infected triatomine bugs, congenital, blood transfusion, organ transplantation, or laboratory accident. Chagas disease can be treated with benznidazole (commercially available since May 14, 2018) or nifurtimox (2). Before January 25, 2021, nifurtimox (Lampit) had been exclusively available through CDC under an Institutional Review Board-approved Investigational New Drug (IND) treatment protocol, at which time it became reasonably accessible to health care providers outside of the program. This report summarizes CDC Drug Service reports for selected characteristics of and adverse events reported by 336 patients for whom nifurtimox was requested under the CDC IND program during January 1, 2001-January 25, 2021. Of the 336 patients, 34.2% resided in California. Median age of patients was 37 years (range = 1-78 years). Most patients were aged 18 (91.8%; 305 of 332) and Hispanic (93.2%; 290 of 311). Among the patients with available information, 91.4% (222 of 243) reported an adverse event. Among those with information about the severity of their adverse events, 20.5% reported a severe event. On August 7, 2020, the Food and Drug Administration (FDA) announced approval of a nifurtimox product, Lampit (Bayer), for treatment of Chagas disease in patients aged <18 years weighing 5.5 lbs (2.5 kg). Lampit became commercially available during October 2020. Physicians should take frequency of adverse events into consideration when prescribing nifurtimox and counseling patients.

Isolation is recommended during acute infection with SARS-CoV-2, the virus that causes COVID-19, but the duration of infectiousness varies among individual persons. Rapid antigen test results have been correlated with detection of viable virus (1-3) and might inform isolation guidance, but data are limited for the recently emerged SARS-CoV-2 B.1.1.529 (Omicron) variant. On January 5, 2022, the Yukon-Kuskokwim Health Corporation (YKHC) recommended that persons with SARS-CoV-2 infection isolate for 10 days after symptom onset (or, for asymptomatic persons, 10 days after a positive nucleic acid amplification or antigen test result). However, isolation could end after 5-9 days if symptoms were resolving or absent, fever was absent for 24 hours without fever-reducing medications, and an Abbott BinaxNOW COVID-19 Ag (BinaxNOW) rapid antigen test result was negative. Antigen test results and associated individual characteristics were analyzed among 3,502 infections reported to YKHC during January 1-February 9, 2022. After 5-9 days, 396 of 729 persons evaluated (54.3%) had a positive antigen test result, with a declining percentage positive over time. In a multivariable model, a positive antigen test result was more likely after 5 days compared with 9 days (adjusted odds ratio [aOR]=6.39) or after symptomatic infection (aOR=9.63), and less likely after previous infection (aOR=0.30), receipt of a primary COVID-19 vaccination series (aOR=0.60), or after both previous infection and receipt of a primary COVID-19 vaccination series (aOR=0.17). Antigen tests might be a useful tool to guide recommendations for isolation after SARS-CoV-2 infection. During the 10 days after infection, persons might be infectious to others and are recommended to wear a well-fitting mask when around others, even if ending isolation after 5 days.

The COVID-19 pandemic has disproportionately affected tribal populations, including the San Carlos Apache Tribe. Universal screening testing in a community using rapid antigen tests could allow for near-real-time identification of COVID-19 cases and result in reduced SARS-CoV-2 transmission. Published experiences of such testing strategies in tribal communities are lacking. Accordingly, tribal partners, with support from the Centers for Disease Control and Prevention, implemented a serial testing program using the Abbott BinaxNOW rapid antigen test in 2 tribal casinos and 1 detention center on the San Carlos Apache Indian Reservation for a 4-week pilot period from January to February 2021. Staff members at each setting, and incarcerated adults at the detention center, were tested every 3 or 4 days with BinaxNOW. During the 4-week period, 3834 tests were performed among 716 participants at the sites. Lessons learned from implementing this program included demonstrating (1) the plausibility of screening testing programs in casino and prison settings, (2) the utility of training non-laboratory personnel in rapid testing protocols that allow task shifting and reduce the workload on public health employees and laboratory staff, (3) the importance of building and strengthening partnerships with representatives from the community and public and private sectors, and (4) the need to implement systems that ensure confidentiality of test results and promote compliance among participants. Our experience and the lessons learned demonstrate that a serial rapid antigen testing strategy may be useful in work settings during the COVID-19 pandemic as schools and businesses are open for service.