Last data update: Nov 22, 2024. (Total: 48197 publications since 2009)
Records 1-30 (of 151 Records) |
Query Trace: Kirby A[original query] |
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Level of involvement of four selected cytochrome P450s (CYPs) in pyrethroid-resistant Anopheles gambiae (s.s.) and Anopheles coluzzii across Côte d'Ivoire
Chabi J , Edi CVA , Kouassi BL , Gbalegba CNG , Kouassi AE , Kouame JKI , Kadio YKA , Yokoly FN , Golou LB , Gouaméné J , Assamoi JB , Tia E , Yapo RM , Konan LY , N'Tamon RN , Koffi AA , Tanoh AM , Ging-Cissé N , Zinzindohoué P , Kouadio B , Yepassis-Zembrou PL , Irish SR , Flatley C , Kirby M . Curr Res Parasitol Vector-Borne Dis 2024 6 In Côte d'Ivoire, there is a high intensity of pyrethroid resistance in malaria vectors which may threaten successful vector control. Molecular studies of the target site mutation in the voltage-gated sodium channel (VGSC) 1014F show that the gene frequencies of these mutations are high, widely spread across Côte d'Ivoire, and even fixed in some areas. To further characterize insecticide resistance in Côte d'Ivoire beyond target site mutations, the metabolic resistance mechanism was explored. Overexpression of the metabolic enzyme cytochrome CYP6M2, CYP6P3, CYP6P4, and CYP6P5 was investigated in Anopheles gambiae (s.s.) and An. coluzzii collected from 30 insecticide resistance monitoring sites across the country in 2021 and 2022. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was carried out using RNA-later preserved 60 surviving mosquitoes from each site after phenotypic susceptibility tests. Additionally, a subsample of about 100 mosquitoes from each site was identified to species by PCR, and the frequency of the VGSC 1014F and 1014S was determined. All four CYPs were found to be overexpressed in Côte d'Ivoire with at least one CYP statistically significantly overexpressed in 27 of the 30 sites investigated compared to the susceptible An. gambiae (s.s.) Kisumu (P < 0.005). CYP6M2 was overexpressed in 89% of sites and was the sole overexpressed gene in 10 sites, while the overexpression of CYP6P3 was found in only 10 sites. CYP6P4 and CYP6P5 were overexpressed in 16 and 13 sites, respectively. Furthermore, seven sites (Adzopé, Bongouanou, Daloa, Gagnoa, Guiglo Jacqueville, and Sassandra) had overexpression of all four CYPs. Overall, An. coluzzii showed higher overexpression of CYPs than An. gambiae (s.s.). This study highlights the involvement of selected CYPs in insecticide resistance where target site mutation genes are already present, suggesting that insecticide resistance is complex and multifaceted at a molecular level. Where feasible, it may be helpful to include metabolic resistance surveillance to further characterize insecticide resistance. © 2024 The Authors |
Norovirus acute gastroenteritis amongst US and European travellers to areas of moderate to high risk of travellers' diarrhoea: A prospective cohort study
Alberer M , Moe CL , Hatz C , Kling K , Kirby AE , Lindsay L , Nothdurft HD , Riera-Montes M , Steffen R , Verstraeten T , Wu HM , DuPont HL . J Travel Med 2024 31 (7) BACKGROUND: Acute gastroenteritis (AGE) is a major medical condition for travellers worldwide, particularly travellers to low- and middle-income countries. Norovirus (NoV) is the most common cause of viral AGE in older children and adults, but data on prevalence and impact amongst travellers is limited. METHODS: Prospective, multi-site, observational cohort study conducted 2015-2017, amongst adult international travellers from the US and Europe to areas of moderate to high risk of travel-acquired AGE. Participants provided self-collected pre-travel stool samples and self-reported AGE symptoms whilst travelling. Post-travel stool samples were requested from symptomatic subjects and a sample of asymptomatic travellers within 14 days of return. Samples were tested for NoV by RT-qPCR, genotyped if positive and tested for other common enteric pathogens by Luminex xTAG GPP. RESULTS: Of the 1109 participants included, 437 (39.4%) developed AGE symptoms resulting in an overall AGE incidence of 24.7 per 100 person-weeks [95% confidence interval (CI): 22.4; 27.1]. In total, 20 NoV-positive AGE cases (5.2% of those tested) were identified at an incidence of 1.1 per 100 person-weeks (95% CI: 0.7; 1.7). NoV-positive samples belonged mostly to genogroup GII (18, 85.7%); None of the 13 samples sequenced belonged to genotype GII.4. Clinical severity of AGE was higher for NoV-positive than for NoV-negative cases (mean modified Vesikari Score 6.8 vs 4.9) with more cases classified as severe or moderate (25% vs 6.8%). In total, 80% of NoV-positive participants (vs 38.9% in NoV-negative) reported at least moderate impact on travel plans. CONCLUSIONS: AGE is a prevalent disease amongst travellers with a small proportion associated with NoV. Post-travel stool sample collection timing might have influenced the low number of NoV cases detected; however, NoV infections resulted in high clinical severity and impact on travel plans. These results may contribute to targeted vaccine development and the design of future studies on NoV epidemiology. |
Discriminating north American swine influenza viruses with a portable, one-step, triplex real-time RT-PCR assay, and portable sequencing
Kirby MK , Shu B , Keller MW , Wilson MM , Rambo-Martin BL , Jang Y , Liddell J , Salinas Duron E , Nolting JM , Bowman AS , Davis CT , Wentworth DE , Barnes JR . Viruses 2024 16 (10) Swine harbors a genetically diverse population of swine influenza A viruses (IAV-S), with demonstrated potential to transmit to the human population, causing outbreaks and pandemics. Here, we describe the development of a one-step, triplex real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay that detects and distinguishes the majority of the antigenically distinct influenza A virus hemagglutinin (HA) clades currently circulating in North American swine, including the IAV-S H1 1A.1 (α), 1A.2 (β), 1A.3 (γ), 1B.2.2 (δ1) and 1B.2.1 (δ2) clades, and the IAV-S H3 2010.1 clade. We performed an in-field test at an exhibition swine show using in-field viral concentration and RNA extraction methodologies and a portable real-time PCR instrument, and rapidly identified three distinct IAV-S clades circulating within the N.A. swine population. Portable sequencing is used to further confirm the results of the in-field test of the swine triplex assay. The IAV-S triplex rRT-PCR assay can be easily transported and used in-field to characterize circulating IAV-S clades in North America, allowing for surveillance and early detection of North American IAV-S with human outbreak and pandemic potential. |
Anopheles gambiae re-emergence and resurgent malaria transmission in Eastern Rwanda, 2010-2020
Hennessee I , Mutabazi A , Munyakanage D , Kabera M , Mbituyumuremyi A , Lucchi N , Kirby MA , Waller LA , Clasen TF , Kitron U , Hakizimana E . Am J Trop Med Hyg 2024 Rwanda achieved unprecedented malaria control gains from 2000 to 2010, but cases increased 20-fold between 2011 and 2017. Vector control challenges and environmental changes were noted as potential explanations, but no studies have investigated causes of the resurgence or identified which vector species drove transmission. We conducted a retrospective study in four sites in eastern Rwanda that conducted monthly entomological surveillance and outpatient malaria care. We compared sporozoite rates, human blood index (HBI), and relative abundance of the primary vectors, Anopheles gambiae and Anopheles arabiensis, from 2017 to 2020. We then modeled the effects of vector control interventions, insecticide resistance, and temperature changes on species composition and reported malaria incidence. Sporozoite rates were 28 times higher and HBI was four times higher in An. gambiae compared with An. arabiensis. Insecticide-treated bed nets, first distributed nationally in 2010, were associated with decreased An. gambiae relative abundance. However, increased pyrethroid resistance was associated with increased An. gambiae relative abundance and malaria incidence. Epidemic malaria peaks corresponded to periods of model-predicted An. gambiae re-emergence, and increased regional air temperatures during the period were further associated with increased malaria incidence. Indoor residual spraying (IRS), implemented with non-pyrethroid insecticides later in the period, was associated with 86% reductions in An. gambiae relative abundance and 75% reductions in malaria incidence. These findings suggest that increased pyrethroid resistance and the re-emergence of An. gambiae were closely linked to the malaria resurgence in eastern Rwanda. Non-pyrethroid IRS or other control measures that effectively target An. gambiae may help prevent future resurgences. |
Wastewater surveillance for influenza A virus and H5 subtype concurrent with the highly pathogenic avian influenza A(H5N1) virus outbreak in cattle and poultry and associated human cases - United States, May 12-July 13, 2024
Louis S , Mark-Carew M , Biggerstaff M , Yoder J , Boehm AB , Wolfe MK , Flood M , Peters S , Stobierski MG , Coyle J , Leslie MT , Sinner M , Nims D , Salinas V , Lustri L , Bojes H , Shetty V , Burnor E , Rabe A , Ellison-Giles G , Yu AT , Bell A , Meyer S , Lynfield R , Sutton M , Scholz R , Falender R , Matzinger S , Wheeler A , Ahmed FS , Anderson J , Harris K , Walkins A , Bohra S , O'Dell V , Guidry VT , Christensen A , Moore Z , Wilson E , Clayton JL , Parsons H , Kniss K , Budd A , Mercante JW , Reese HE , Welton M , Bias M , Webb J , Cornforth D , Santibañez S , Soelaeman RH , Kaur M , Kirby AE , Barnes JR , Fehrenbach N , Olsen SJ , Honein MA . MMWR Morb Mortal Wkly Rep 2024 73 (37) 804-809 As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season. |
Cluster of influenza A(H5) cases associated with poultry exposure at two facilities - Colorado, July 2024
Drehoff CC , White EB , Frutos AM , Stringer G , Burakoff A , Comstock N , Cronquist A , Alden N , Armistead I , Kohnen A , Ratnabalasuriar R , Travanty EA , Matzinger SR , Rossheim A , Wellbrock A , Pagano HP , Wang D , Singleton J , Sutter RA , Davis CT , Kniss K , Ellington S , Kirby MK , Reed C , Herlihy R . MMWR Morb Mortal Wkly Rep 2024 73 (34) 734-739 Persons who work in close contact with dairy cattle and poultry that are infected with highly pathogenic avian influenza (HPAI) A(H5N1) virus are at increased risk for infection. In July 2024, the Colorado Department of Public Health & Environment responded to two poultry facilities with HPAI A(H5N1) virus detections in poultry. Across the two facilities, 663 workers assisting with poultry depopulation (i.e., euthanasia) received screening for illness; 109 (16.4%) reported symptoms and consented to testing. Among those who received testing, nine (8.3%) received a positive influenza A(H5) virus test result, and 19 (17.4%) received a positive SARS-CoV-2 test result. All nine workers who received positive influenza A(H5) test results had conjunctivitis, experienced mild illness, and received oseltamivir. This poultry exposure-associated cluster of human cases of influenza A(H5) is the first reported in the United States. The identification of these cases highlights the ongoing risk to persons who work in close contact with infected animals. Early response to each facility using multidisciplinary, multilingual teams facilitated case-finding, worker screening, and treatment. As the prevalence of HPAI A(H5N1) virus clade 2.3.4.4b genotype B3.13 increases, U.S. public health agencies should prepare to rapidly investigate and respond to illness in agricultural workers, including workers with limited access to health care. |
Influenza A(H5N1) virus infection in two dairy farm workers in Michigan
Morse J , Coyle J , Mikesell L , Stoddard B , Eckel S , Weinberg M , Kuo J , Riner D , Margulieux K , Stricklen J , Dover M , Kniss KL , Jang Y , Kirby MK , Frederick JC , Lacek KA , Davis CT , Uyeki TM , Lyon-Callo S , Bagdasarian N . N Engl J Med 2024 |
Rabies surveillance in the United States during 2022
Ma X , Boutelle C , Bonaparte S , Orciari LA , Condori RE , Kirby JD , Chipman RB , Fehlner-Gardiner C , Thang C , Cedillo VG , Aréchiga-Ceballos N , Nakazawa Y , Wallace RM . J Am Vet Med Assoc 2024 1-8 OBJECTIVE: To provide comprehensive epidemiological information about the distribution and occurrence of rabies during 2022 in the US, Canada, and Mexico. METHODS: The US National Rabies Surveillance System collected 2022 animal rabies data from US state and territorial public health departments and USDA Wildlife Services. Temporal and geographic analyses were conducted to evaluate trends in animal rabies cases. RESULTS: During 2022, 54 US jurisdictions reported 3,579 animal rabies cases, reflecting a 2.3% decline from 3,663 cases reported in 2021. Six states collectively reported > 50% of animal rabies cases: Texas (395 [11.0%]), Virginia (337 [9.4%]), Pennsylvania (329 [9.2%]), New York (267 [7.5%]), North Carolina (264 [7.4%]), and California (241 [6.7%]). Out of the total reported rabies animal cases, 3,234 (90.4%) were attributed to wildlife, with bats (1,218 [34.0%]), raccoons (1,014 [28.3%]), skunks (660 [18.4%]), and foxes (269 [7.5%]) representing the primary hosts confirmed with rabies. Rabid cats (222 [6.2%]), cattle (42 [1.2%]), and dogs (50 [1.4%]) constituted > 90% of reported domestic animal rabies cases. CONCLUSIONS: In 2022, there was an increase in the number of animal samples submitted for rabies testing in the US and Canada. A notable geographic expansion of gray fox rabies virus variant was detected in the US. Three human rabies deaths due to vampire bat rabies infection occurred in Mexico; none were reported from the US and Canada. CLINICAL RELEVANCE: Laboratory diagnosis of rabies in animals is critical to ensure judicious use of human rabies postexposure prophylaxis. |
Genetic tracking of a rabid coyote (Canis latrans) detected beyond a rabies enzootic area in West Virginia, US
Hopken MW , Gigante C , Gilbert AT , Chipman RB , Kirby JD , Condori RE , Mills S , Hartley C , Forbes J , Dettinger L , Xia D , Li Y , vonHoldt B . J Wildl Dis 2024 60 (3) 745-752 Wildlife translocation and cross-species transmission can impede control and elimination of emerging zoonotic diseases. Tracking the geographic origin of both host and virus (i.e., translocation versus local infection) may help determine the most effective response when high-risk cases of emerging pathogens are identified in wildlife. In May 2022, a coyote (Canis latrans) infected with the raccoon (Procyon lotor) rabies virus variant (RRV) was collected in Lewis County, West Virginia, USA, an area free from RRV. We applied host population genomics and RRV phylogenetic analyses to determine the most likely geographic origin of the rabid coyote. Coyote genomic analyses included animals from multiple eastern states bordering West Virginia, with the probable origin of the rabid coyote being the county of collection. The RRV phylogenetic analyses included cases detected from West Virginia and neighboring states, with most similar RRV sequences collected in a county 80 km to the northeast, within the oral rabies vaccination zone. The combined results suggest that the coyote was infected in an RRV management area and carried the RRV to Lewis County, a pattern consistent with coyote local movement ecology. Distant cross-species transmission and subsequent host movement presents a low risk for onward transmission in raccoon populations. This information helped with emergency response decision-making, thereby saving time and resources. |
Outbreak of highly pathogenic avian influenza A(H5N1) viruses in U.S. dairy cattle and detection of two human cases - United States, 2024
Garg S , Reed C , Davis CT , Uyeki TM , Behravesh CB , Kniss K , Budd A , Biggerstaff M , Adjemian J , Barnes JR , Kirby MK , Basler C , Szablewski CM , Richmond-Crum M , Burns E , Limbago B , Daskalakis DC , Armstrong K , Boucher D , Shimabukuro TT , Jhung MA , Olsen SJ , Dugan V . MMWR Morb Mortal Wkly Rep 2024 73 (21) 501-505 |
Antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S. Throughout the Delta to Omicron waves
Di H , Pusch EA , Jones J , Kovacs NA , Hassell N , Sheth M , Lynn KS , Keller MW , Wilson MM , Keong LM , Cui D , Park SH , Chau R , Lacek KA , Liddell JD , Kirby MK , Yang G , Johnson M , Thor S , Zanders N , Feng C , Surie D , DeCuir J , Lester SN , Atherton L , Hicks H , Tamin A , Harcourt JL , Coughlin MM , Self WH , Rhoads JP , Gibbs KW , Hager DN , Shapiro NI , Exline MC , Lauring AS , Rambo-Martin B , Paden CR , Kondor RJ , Lee JS , Barnes JR , Thornburg NJ , Zhou B , Wentworth DE , Davis CT . Vaccines (Basel) 2024 12 (5) Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates. |
U.S. preparedness and response to increasing clade I mpox cases in the Democratic Republic of the Congo - United States, 2024
McQuiston JH , Luce R , Kazadi DM , Bwangandu CN , Mbala-Kingebeni P , Anderson M , Prasher JM , Williams IT , Phan A , Shelus V , Bratcher A , Soke GN , Fonjungo PN , Kabamba J , McCollum AM , Perry R , Rao AK , Doty J , Christensen B , Fuller JA , Baird N , Chaitram J , Brown CK , Kirby AE , Fitter D , Folster JM , Dualeh M , Hartman R , Bart SM , Hughes CM , Nakazawa Y , Sims E , Christie A , Hutson CL . MMWR Morb Mortal Wkly Rep 2024 73 (19) 435-440 Clade I monkeypox virus (MPXV), which can cause severe illness in more people than clade II MPXVs, is endemic in the Democratic Republic of the Congo (DRC), but the country has experienced an increase in suspected cases during 2023-2024. In light of the 2022 global outbreak of clade II mpox, the increase in suspected clade I cases in DRC raises concerns that the virus could spread to other countries and underscores the importance of coordinated, urgent global action to support DRC's efforts to contain the virus. To date, no cases of clade I mpox have been detected outside of countries in Central Africa where the virus is endemic. CDC and other partners are working to support DRC's response. In addition, CDC is enhancing U.S. preparedness by raising awareness, strengthening surveillance, expanding diagnostic testing capacity for clade I MPXV, ensuring appropriate specimen handling and waste management, emphasizing the importance of appropriate medical treatment, and communicating guidance on the recommended contact tracing, containment, behavior modification, and vaccination strategies. |
Sentinel laboratory compliance with best practices in Burkina Faso's antimicrobial resistance surveillance network
Yenyetou D , Zongo E , Dama E , Muhigwa M , Sanou I , Sawadogo C , Ouangraoua S , Sangare I , Nikiema A , Dahourou AG , Ouedraogo AS . Afr J Lab Med 2024 13 (1) 2259 BACKGROUND: Standardising procedures is the best way to harmonise and strengthen the quality of laboratory-based antimicrobial resistance surveillance. Since 2018, Burkina Faso has developed and disseminated the national manual of procedures for performing antibiotic susceptibility tests in sentinel laboratories within its national antimicrobial resistance surveillance network. OBJECTIVE: Our study aimed to assess these sentinel laboratories' compliance with good practices for antibiotics susceptibility tests. METHODS: Four teams evaluated the antimicrobial resistance sentinel sites laboratories throughout Burkina Faso from 19 to 28 September 2022. Eighteen out of 19 sentinel laboratories were evaluated. A four-member technical committee designed and validated the evaluation tool composed of three Microsoft Excel sheets. The evaluation emphasised quality controls for culture media, antibiotic discs and compliance with antimicrobial susceptibility testing procedures by the laboratories. Excel software was used for data recording and graphs and table design. The free R software version 4.2.0 was used for descriptive statistics. An overall score below 80% was considered noncompliance. RESULTS: Most (83.33%) of the sentinel laboratories conducted at least one quality control activity for culture media, and 66.67% conducted at least one quality control activity for antibiotic discs. Over three-quarters (76.47%) of the laboratories were more than 80% compliant with the modified Kirby Bauer antimicrobial susceptibility testing method. CONCLUSION: The evaluation revealed the noncompliance of sentinel laboratories with the national procedure manual, particularly in the quality control component. WHAT THIS STUDY ADDS: This study has provided baseline data on the sentinel laboratories' compliance with the national antimicrobial susceptibility testing procedures manual, particularly in areas performing quality control checks or meeting quality indicators for culture media and antibiotic discs. |
Highly pathogenic avian influenza A(H5N1) virus infection in a dairy farm worker
Uyeki TM , Milton S , Abdul Hamid C , Reinoso Webb C , Presley SM , Shetty V , Rollo SN , Martinez DL , Rai S , Gonzales ER , Kniss KL , Jang Y , Frederick JC , De La Cruz JA , Liddell J , Di H , Kirby MK , Barnes JR , Davis CT . N Engl J Med 2024 |
The National Wastewater Surveillance System (NWSS): From inception to widespread coverage, 2020-2022, United States
Adams C , Bias M , Welsh RM , Webb J , Reese H , Delgado S , Person J , West R , Shin S , Kirby A . Sci Total Environ 2024 171566 Wastewater surveillance is a valuable tool that can be used to track infectious diseases in a community. In September 2020, the Centers for Disease Control and Prevention (CDC) established the National Wastewater Surveillance System (NWSS) to coordinate and build the nation's capacity to detect and quantify concentrations of SARS-CoV-2 RNA in U.S. wastewater. This is the first surveillance summary of NWSS, covering September 1, 2020 to December 31, 2022. Through partnerships with state, tribal, local, and territorial health departments, NWSS became a national surveillance platform that can be readily expanded and adapted to meet changing public health needs. Beginning with 209 sampling sites in September 2020, NWSS rapidly expanded to >1500 sites by December 2022, covering ≈47 % of the U.S. population. As of December 2022, >152,000 unique wastewater samples have been collected by NWSS partners, primarily from wastewater treatment plants (WWTPs). WWTPs participating in NWSS tend to be larger than the average U.S. WWTP and serve more populated communities. In December 2022, ≈8 % of the nearly 16,000 U.S. WWTPs were participating in NWSS. NWSS partners used a variety of methods for sampling and testing wastewater samples; however, progress is being made to standardize these methods. In July 2021, NWSS partners started submitting SARS-CoV-2 genome sequencing data to NWSS. In October 2022, NWSS expanded to monkeypox virus testing, with plans to include additional infectious disease targets in the future. Through the rapid implementation and expansion of NWSS, important lessons have been learned. Wastewater surveillance programs should consider both surge and long-term capacities when developing an implementation plan, and early standardization of sampling and testing methods is important to facilitate data comparisons across sites. NWSS has proven to be a flexible and sustainable surveillance system that will continue to be a useful complement to case-based surveillance for guiding public health action. |
Evaluation of contingency actions to control the spread of raccoon rabies in Ohio and Virginia
Davis AJ , Chipman RB , Nelson KM , Haley BS , Kirby JD , Ma X , Wallace RM , Gilbert AT . Prev Vet Med 2024 225 106145 The raccoon (Procyon lotor) variant of the rabies virus (RRV) is enzootic in the eastern United States and oral rabies vaccination (ORV) is the primary strategy to prevent and control landscape spread. Breaches of ORV management zones occasionally occur, and emergency "contingency" actions may be implemented to enhance local control. Contingency actions are an integral part of landscape-scale wildlife rabies management but can be very costly and routinely involve enhanced rabies surveillance (ERS) around the index case. We investigated two contingency actions in Ohio (2017-2019 and 2018-2021) and one in Virginia (2017-2019) using a dynamic, multi-method occupancy approach to examine relationships between specific management actions and RRV occurrence, including whether ERS was sufficient around the index case. The RRV occupancy was assessed seasonally at 100-km(2) grids and we examined relationships across three spatial scales (regional management zone, RRV free regions, and local contingency areas). The location of a grid relative to the ORV management zone was the strongest predictor of RRV occupancy at the regional scale. In RRV free regions, the neighbor effect and temporal variability were most important in influencing RRV occupancy. Parenteral (hand) vaccination of raccoons was important across all three contingency action areas, but more influential in the Ohio contingency action areas where more raccoons were hand vaccinated. In the Virginia contingency action area, ORV strategies were as important in reducing RRV occupancy as a hand vaccination strategy. The management action to trap, euthanize, and test (TET) raccoons was an important method to increase ERS, yet the impacts of TET on RRV occupancy are not clear. The probability of detecting additional cases of RRV was exceptionally high (>0.95) during the season the index case occurred. The probability of detecting RRV through ERS declined in the seasons following initial TET efforts but remained higher after the contingency action compared to the ERS detection probabilities prior to index case incidence. Local RRV cases were contained within one year and eliminated within 2-3 years of each contingency action. |
National population-based estimates for major birth defects, 2016-2020
Stallings EB , Isenburg JL , Rutkowski RE , Kirby RS , Nembhard WN , Sandidge T , Villavicencio S , Nguyen HH , McMahon DM , Nestoridi E , Pabst LJ . Birth Defects Res 2024 116 (1) e2301 BACKGROUND: We provide updated crude and adjusted prevalence estimates of major birth defects in the United States for the period 2016-2020. METHODS: Data were collected from 13 US population-based surveillance programs that used active or a combination of active and passive case ascertainment methods to collect all birth outcomes. These data were used to calculate pooled prevalence estimates and national prevalence estimates adjusted for maternal race/ethnicity for all conditions, and maternal age for trisomies and gastroschisis. Prevalence was compared to previously published national estimates from 1999 to 2014. RESULTS: Adjusted national prevalence estimates per 10,000 live births ranged from 0.63 for common truncus to 18.65 for clubfoot. Temporal changes were observed for several birth defects, including increases in the prevalence of atrioventricular septal defect, tetralogy of Fallot, omphalocele, trisomy 18, and trisomy 21 (Down syndrome) and decreases in the prevalence of anencephaly, common truncus, transposition of the great arteries, and cleft lip with and without cleft palate. CONCLUSION: This study provides updated national estimates of selected major birth defects in the United States. These data can be used for continued temporal monitoring of birth defects prevalence. Increases and decreases in prevalence since 1999 observed in this study warrant further investigation. |
Detecting Mpox cases through wastewater surveillance - United States, August 2022-May 2023
Adams C , Kirby AE , Bias M , Riser A , Wong KK , Mercante JW , Reese H . MMWR Morb Mortal Wkly Rep 2024 73 (2) 37-43 In October 2022, CDC's National Wastewater Surveillance System began routine testing of U.S. wastewater for Monkeypox virus. Wastewater surveillance sensitivity, positive predictive value (PPV), and negative predictive value (NPV) for Monkeypox virus were evaluated by comparing wastewater detections (Monkeypox virus detected versus not detected) to numbers of persons with mpox in a county who were shedding virus. Case ascertainment was assumed to be complete, and persons with mpox were assumed to shed virus for 25 days after symptom onset. A total of 281 cases and 3,492 wastewater samples from 89 sites in 26 counties were included in the analysis. Wastewater surveillance in a single week, from samples representing thousands to millions of persons, had a sensitivity of 32% for detecting one or more persons shedding Monkeypox virus, 49% for detecting five or more persons shedding virus, and 77% for detecting 15 or more persons shedding virus. Weekly PPV and NPV for detecting persons shedding Monkeypox virus in a county were 62% and 80%, respectively. An absence of detections in counties with wastewater surveillance signified a high probability that a large number of cases were not present. Results can help to guide the public health response to Monkeypox virus wastewater detections. A single, isolated detection likely warrants a limited public health response. An absence of detections, in combination with no reported cases, can give public health officials greater confidence that no cases are present. Wastewater surveillance can serve as a useful complement to case surveillance for guiding the public health response to an mpox outbreak. |
Novel strain of multidrug non-susceptible Neisseria gonorrhoeae in the USA
Reimche JL , Pham CD , Joseph SJ , Hutton S , Cartee JC , Ruan Y , Breaux M , Ivanof C , Joshi A , DeMartino M , Kirby JE , Barbee LA , Kersh EN , Roosevelt KA , Hsu KK . Lancet Infect Dis 2024 Unsuccessful treatment of gonorrhoea has not yet occurred in the USA, and cases of gonorrhoea that are non-susceptible to cephalosporins have been rare. In 2019, non-susceptibility to ceftriaxone conferred by the mosaic penA 60.001 allele was found in a Neisseria gonorrhoeae multilocus sequence type (MLST) 1901 isolate from Nevada.1 In this Correspondence, we present two additional US cases of the penA 60.001 allele identified in MLST 8123, an emerging international multidrug non-susceptible N gonorrhoeae lineage. Although these cases responded to ceftriaxone treatment, N gonorrhoeae isolates from the first known patient (case 1) demonstrated in-vitro non-susceptibility to ceftriaxone as well as non-susceptibility or resistance to drugs previously recommended for front-line treatment. | | In August, 2022, N gonorrhoeae grown from urine culture from a patient with urethritis in primary care in Massachusetts displayed non-susceptibility to cephalosporins (the minimum inhibitory concentrations were 1·0 μg/mL for ceftriaxone and >1·0 μg/mL for cefixime by agar dilution; the minimum inhibitory concentration for cefixime was 1·5 μg/mL by gradient strip) and azithromycin and resistance to ciprofloxacin, penicillin, and tetracycline (appendix pp 6–7). Antimicrobial susceptibility testing was done with gradient strips at the state public health laboratory Massachusetts and then confirmed via agar dilution at the US Centers for Disease Control and Prevention (CDC). The patient (case 1) had already been successfully diagnosed on nucleic acid amplification test (NAAT) with gonorrhoea and was given 500 mg ceftriaxone intramuscularly and asked to return to primary care where, 9 days after treatment, he was asymptomatic, had normal results during examination, and tested negative by urine culture and pharyngeal and rectal NAAT recommended by the Massachusetts sexually transmitted diseases programme to document N gonorrhoeae clearance from any site of infection. The patient reported that he had not travelled outside USA in the 60 days before onset of symptoms. He disclosed female sex worker contacts, but insufficient information was provided to trace the contacts. |
In-field detection and characterization of B/Victoria lineage deletion variant viruses causing early influenza activity and an outbreak in Louisiana, 2019
Shu B , Wilson MM , Keller MW , Tran H , Sokol T , Lee G , Rambo-Martin BL , Kirby MK , Hassell N , Haydel D , Hand J , Wentworth DE , Barnes JR . Influenza Other Respir Viruses 2024 18 (1) e13246 BACKGROUND: In 2019, the Louisiana Department of Health reported an early influenza B/Victoria (B/VIC) virus outbreak. METHOD: As it was an atypically large outbreak, we deployed to Louisiana to investigate it using genomics and a triplex real-time RT-PCR assay to detect three antigenically distinct B/VIC lineage variant viruses. RESULTS: The investigation indicated that B/VIC V1A.3 subclade, containing a three amino acid deletion in the hemagglutinin and known to be antigenically distinct to the B/Colorado/06/2017 vaccine virus, was the most prevalent circulating virus within the specimens evaluated (86/88 in real-time RT-PCR). CONCLUSION: This work underscores the value of portable platforms for rapid, onsite pathogen characterization. |
Targeted amplification and genetic sequencing of the severe acute respiratory syndrome coronavirus 2 surface glycoprotein
Keller MW , Keong LM , Rambo-Martin BL , Hassell N , Lacek KA , Wilson MM , Kirby MK , Liddell J , Owuor DC , Sheth M , Madden J , Lee JS , Kondor RJ , Wentworth DE , Barnes JR . Microbiol Spectr 2023 e0298223 The COVID-19 pandemic was accompanied by an unprecedented surveillance effort. The resulting data were and will continue to be critical for surveillance and control of SARS-CoV-2. However, some genomic surveillance methods experienced challenges as the virus evolved, resulting in incomplete and poor quality data. Complete and quality coverage, especially of the S-gene, is important for supporting the selection of vaccine candidates. As such, we developed a robust method to target the S-gene for amplification and sequencing. By focusing on the S-gene and imposing strict coverage and quality metrics, we hope to increase the quality of surveillance data for this continually evolving gene. Our technique is currently being deployed globally to partner laboratories, and public health representatives from 79 countries have received hands-on training and support. Expanding access to quality surveillance methods will undoubtedly lead to earlier detection of novel variants and better inform vaccine strain selection. |
Author Correction: Multiplexed CRISPR-based microfluidic platform for clinical testing of respiratory viruses and identification of SARS-CoV-2 variants
Welch NL , Zhu M , Hua C , Weller J , Mirhashemi ME , Nguyen TG , Mantena S , Bauer MR , Shaw BM , Ackerman CM , Thakku SG , Tse MW , Kehe J , Uwera MM , Eversley JS , Bielwaski DA , McGrath G , Braidt J , Johnson J , Cerrato F , Moreno GK , Krasilnikova LA , Petros BA , Gionet GL , King E , Huard RC , Jalbert SK , Cleary ML , Fitzgerald NA , Gabriel SB , Gallagher GR , Smole SC , Madoff LC , Brown CM , Keller MW , Wilson MM , Kirby MK , Barnes JR , Park DJ , Siddle KJ , Happi CT , Hung DT , Springer M , MacInnis BL , Lemieux JE , Rosenberg E , Branda JA , Blainey PC , Sabeti PC , Myhrvold C . Nat Med 2023 In the version of the article originally published, some of the oligonucleotide sequences in Supplementary Table 4, on the “21 viruses” and “RVP” tabs, were mislabeled. The Supplementary Tables file has now been corrected. |
Early detection and surveillance of the SARS-CoV-2 variant BA.2.86 - Worldwide, July-October 2023
Lambrou AS , South E , Ballou ES , Paden CR , Fuller JA , Bart SM , Butryn DM , Novak RT , Browning SD , Kirby AE , Welsh RM , Cornforth DM , MacCannell DR , Friedman CR , Thornburg NJ , Hall AJ , Hughes LJ , Mahon BE , Daskalakis DC , Shah ND , Jackson BR , Kirking HL . MMWR Morb Mortal Wkly Rep 2023 72 (43) 1162-1167 Early detection of emerging SARS-CoV-2 variants is critical to guiding rapid risk assessments, providing clear and timely communication messages, and coordinating public health action. CDC identifies and monitors novel SARS-CoV-2 variants through diverse surveillance approaches, including genomic, wastewater, traveler-based, and digital public health surveillance (e.g., global data repositories, news, and social media). The SARS-CoV-2 variant BA.2.86 was first sequenced in Israel and reported on August 13, 2023. The first U.S. COVID-19 case caused by this variant was reported on August 17, 2023, after a patient received testing for SARS-CoV-2 at a health care facility on August 3. In the following month, eight additional U.S. states detected BA.2.86 across various surveillance systems, including specimens from health care settings, wastewater surveillance, and traveler-based genomic surveillance. As of October 23, 2023, sequences have been reported from at least 32 countries. Continued variant tracking and further evidence are needed to evaluate the full public health impact of BA.2.86. Timely genomic sequence submissions to global public databases aided early detection of BA.2.86 despite the decline in the number of specimens being sequenced during the past year. This report describes how multicomponent surveillance and genomic sequencing were used in real time to track the emergence and transmission of the BA.2.86 variant. This surveillance approach provides valuable information regarding implementing and sustaining comprehensive surveillance not only for novel SARS-CoV-2 variants but also for future pathogen threats. |
Detection and discrimination of influenza B Victoria lineage deletion variant viruses by real-time RT-PCR (preprint)
Shu B , Kirby MK , Warnes C , Sessions WM , Davis WG , Liu J , Wilson MM , Wentworth DE , Barnes JR . bioRxiv 2019 818617 Influenza B viruses have two genetically and antigenically distinct lineages, B/Victoria/2/1987-like (VIC) and B/Yamagata/16/1988-like (YAM) viruses, that emerged in the 1980s and co-circulate annually during the influenza season. During the 2016-2017 influenza season, influenza B/VIC lineage variant viruses emerged with two (K162N163) or three (K162N163D164) amino acid (AA) deletions in the hemagglutinin protein. Hemagglutination inhibition assays demonstrate that these deletion variant influenza B/VIC viruses are antigenically distinct from each other and from the progenitor B/VIC virus that lacks the deletion. Therefore, there are currently four antigenically distinct HA proteins expressed by influenza B co-circulating: B/YAM, B/VIC V1A (no deletion), B/VIC V1A.1 (two-AA deletion), and B/VIC V1A.2 and V1A.3 (three-AA deletion). The prevalence of these viruses differs across geographic regions, making it critical to have a sensitive, rapid diagnostic assay(s) that detect and distinguish these Influenza B variant viruses during surveillance. Here, we present a real time RT-PCR assay that targets the influenza B/VIC deletion region in the HA gene and detects and distinguishes the influenza B/VIC V1A, B/VIC V1A.1, B/VIC V1A.2 and B/VIC V1A.3 variant viruses, with no cross-reactivity. This assay can be run as a multiplex reaction, allowing for increased testing efficiency and reduced cost. Coupling this assay with the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel Influenza B Lineage Genotyping Kit results in rapid detection and characterization of circulating influenza B viruses. Having accurate and detailed surveillance information on these distinct Influenza B variant viruses will provide insight into the prevalence and geographic distribution and could aid in vaccine recommendations. |
Efficacy of partial spraying of SumiShield, Fludora Fusion and Actellic against wild populations of Anopheles gambiae s.l. in experimental huts in Tiassal, Cte d'Ivoire
Chabi J , Seyoum A , Edi CVA , Kouassi BL , Yihdego Y , Oxborough R , Gbalegba CGN , Johns B , Desale S , Irish SR , Gimnig JE , Carlson JS , Yoshimizu M , Armistead JS , Belemvire A , Gerberg L , George K , Kirby M . Sci Rep 2023 13 (1) 11364 From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy. |
Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications
Bascom JT , Stephens SB , Lupo PJ , Canfield MA , Kirby RS , Nestoridi E , Salemi JL , Mai CT , Nembhard WN , Forestieri NE , Romitti PA , St Louis AM , Agopian AJ . Birth Defects Res 2023 BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact. METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated. RESULTS: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States. CONCLUSIONS: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care. |
Inpatient hospitalization costs associated with birth defects among persons aged <65 years - United States, 2019
Swanson J , Ailes EC , Cragan JD , Grosse SD , Tanner JP , Kirby RS , Waitzman NJ , Reefhuis J , Salemi JL . MMWR Morb Mortal Wkly Rep 2023 72 (27) 739-745 Changing treatments and medical costs necessitate updates to hospitalization cost estimates for birth defects. The 2019 National Inpatient Sample was used to estimate the service delivery costs of hospitalizations among patients aged <65 years for whom one or more birth defects were documented as discharge diagnoses. In 2019, the estimated cost of these birth defect-associated hospitalizations in the United States was $22.2 billion. Birth defect-associated hospitalizations bore disproportionately high costs, constituting 4.1% of all hospitalizations among persons aged <65 years and 7.7% of related inpatient medical costs. Updating estimates of hospitalization costs provides information about health care resource use associated with birth defects and the financial impact of birth defects across the life span and illustrates the need to determine the continued health care needs of persons born with birth defects to ensure optimal health for all. |
Individualized education programs and transition planning for adolescents with autism
Hughes MM , Kirby AV , Davis J , Bilder DA , Patrick M , Lopez M , DaWalt LS , Pas ET , Bakian AV , Shaw KA , DiRienzo M , Hudson A , Schwenk YD , Baroud TM , Washington A , Maenner MJ . Pediatrics 2023 152 (1) OBJECTIVES: The study objectives were to examine the contents of individualized education programs (IEPs) of adolescents with autism spectrum disorder (ASD), including postsecondary transition goals, services, and changes in special education classification over time. METHODS: This study involved a longitudinal population-based surveillance cohort from the Autism Developmental Disabilities Monitoring Network from 2002 to 2018 in 3 catchment areas in the United States. The sample included 322 adolescents who were born in 2002, identified with ASD, and had an IEP available for review at ages 15-16 years. RESULTS: We found that 297 (92%) adolescents with ASD had an IEP including a transition plan. Those without intellectual disability (ID) were more likely to have postsecondary education and employment goals and have those goals be to pursue higher education or competitive employment compared with those with ID. Forty-one percent of adolescents with ASD had a postsecondary living arrangement goal. Although 28% of adolescents with ASD received school-based mental health services, none of these adolescents were Black; additionally, 15% of those with ID received mental health services compared with 34% without ID. The percentage of adolescents with ASD served under an autism classification increased from 44% at age 8 years to 62% by age 16. CONCLUSIONS: We identified gaps and disparities in school-based postsecondary transition planning. Working with education partners, families, and adolescents will be important to identify what challenges contribute to these findings and what supports are needed to improve the equity and quality of the transition planning process for adolescents with ASD so they are prepared for adulthood. |
COVID-19 surveillance after expiration of the public health emergency declaration - United States, May 11, 2023
Silk BJ , Scobie HM , Duck WM , Palmer T , Ahmad FB , Binder AM , Cisewski JA , Kroop S , Soetebier K , Park M , Kite-Powell A , Cool A , Connelly E , Dietz S , Kirby AE , Hartnett K , Johnston J , Khan D , Stokley S , Paden CR , Sheppard M , Sutton P , Razzaghi H , Anderson RN , Thornburg N , Meyer S , Womack C , Weakland AP , McMorrow M , Broeker LR , Winn A , Hall AJ , Jackson B , Mahon BE , Ritchey MD . MMWR Morb Mortal Wkly Rep 2023 72 (19) 523-528 On January 31, 2020, the U.S. Department of Health and Human Services (HHS) declared, under Section 319 of the Public Health Service Act, a U.S. public health emergency because of the emergence of a novel virus, SARS-CoV-2.* After 13 renewals, the public health emergency will expire on May 11, 2023. Authorizations to collect certain public health data will expire on that date as well. Monitoring the impact of COVID-19 and the effectiveness of prevention and control strategies remains a public health priority, and a number of surveillance indicators have been identified to facilitate ongoing monitoring. After expiration of the public health emergency, COVID-19-associated hospital admission levels will be the primary indicator of COVID-19 trends to help guide community and personal decisions related to risk and prevention behaviors; the percentage of COVID-19-associated deaths among all reported deaths, based on provisional death certificate data, will be the primary indicator used to monitor COVID-19 mortality. Emergency department (ED) visits with a COVID-19 diagnosis and the percentage of positive SARS-CoV-2 test results, derived from an established sentinel network, will help detect early changes in trends. National genomic surveillance will continue to be used to estimate SARS-CoV-2 variant proportions; wastewater surveillance and traveler-based genomic surveillance will also continue to be used to monitor SARS-CoV-2 variants. Disease severity and hospitalization-related outcomes are monitored via sentinel surveillance and large health care databases. Monitoring of COVID-19 vaccination coverage, vaccine effectiveness (VE), and vaccine safety will also continue. Integrated strategies for surveillance of COVID-19 and other respiratory viruses can further guide prevention efforts. COVID-19-associated hospitalizations and deaths are largely preventable through receipt of updated vaccines and timely administration of therapeutics (1-4). |
Changes in spina bifida lesion level after folic acid fortification in the US
Mai CT , Evans J , Alverson CJ , Yue X , Flood T , Arnold K , Nestoridi E , Denson L , Adisa O , Moore CA , Nance A , Zielke K , Rice S , Shan X , Dean JH , Ethen M , Hansen B , Isenburg J , Kirby RS . Obstet Gynecol Surv 2023 78 (4) 189-191 following which a substantial decline in neural tube defects at birth occurred. Studies also have suggested that lesion levels in cases of spina bifida are directly affected by folic acid fortification. Locations of such lesions contribute to outcome and prognosis of the condition. When compared with sacral and lower lumbar lesions, the greatest risks of disability and mortality are associated with cervical, thoracic, and high lumbar lesions. Individuals with thoracic or high lumbar lesions require a wheelchair and orthosis in adulthood for ambulation 70% to 99% of the time. As lesion levels therefore determine function and overall quality of life, assessment of whether folic acid fortification significantly impacts lesion levels is important. This study aimed to examine patterns of lesion levels in spina bifida following mandatory folic acid fortification in the United States. | | A call was issued by the National Birth Defects Prevention Network for State Birth Defects Programs' spina bifida lesion data before and after fortification mandate. To be eligible, programs needed to provide verbatim medical record text descriptions of spina bifida diagnoses. The 6 participating programs were from the states of Arizona, California (covering 8 counties), Oklahoma, South Carolina, Utah, and metropolitan Atlanta (Georgia). Birth years examined included the prefortification years of 1992–1996 and the postfortification period of 1999–2016. Central processing and analysis occurred as each program provided case-level data (deidentified) based on the exclusion/inclusion criteria to the Centers for Disease Control and Prevention. Medical and record text description of the spina bifida diagnosis and codes were the basis of case information, using the International Classification of Diseases, Ninth Edition, Clinical Modification or the Centers for Disease Control and Prevention and Prevention/British Pediatric Association coding system. Types of spina bifida included in the study were spinal rachischisis, myelomeningocele/meningomyelocele, meningocele, and spina bifida not otherwise specified. Cases excluded were cranial lesions, lipomyelomeningocele/lipomeningomyelocele, dysraphism related to split cord malformations, and spina bifida occulta. | | Lesion-level information was provided based on the highest lesion using nonradiographic clinical assessment. Classification of severe upper-level lesions included cervical or thoracic lesion-level cases, whereas lower-level lesions included cases with lumbar or sacral. The study defined open lesion as leaking spinal fluid or membrane covered only, whereas closed lesions were defined as having intact-skin covering and lacking fluid leakage. Spina bifida cases were considered isolated when no other anomalies related to the primary cause of abnormal neural tube closure were present (nor were secondary to the neurologic complications caused by it). Examining associations between fortification period and the outcomes (lesion level and spina bifida) occurred using the generalized estimating approach to logistic (case severity analyses) and log-linear (PR analyses) regression, which accounted for clustering of cases by state. | | From a total of 7,816,062 live births, 2593 cases of spina bifida met the case inclusion criteria. Overall, 573 cases were included in the prefortification period (birth prevalence of 4.07 per 10,000 live births), and 2020 cases were included in the postfortification period (birth prevalence of 3.15 per 10,000 live births). Overall, 80.2% of cases resulted in live births, and most cases of spina bifida involved lower-level lesions (81.3%). Most lesions were lumbar, and the proportions prefortification and postfortification were 61.4% and 72.0%, respectively, with a higher proportion of lumbar lesions seen in the postfortification period. The odds of upper-level to lower-level lesions decreased by 70% after fortification. The spina bifida live birth prevalence decreased significantly and remained consistently low throughout the early, mid, and recent postfortification periods. The study found a 72% decrease overall in prevalence of severe, upper-level lesions following mandatory folic acid fortification in the United States. | | The limitations of the study include the shortcomings of relying on diagnostic codes, the difficulty of coding lesion level using the International Classification of Diseases, Ninth Edition, Clinical Modification coding scheme, the lack of recorded functional outcome for children in medical records (indirect indicators of severity), the lack of preconception and prenatal folic acid data, and the possible variation of case ascertainment within programs contributing studies. A major study strength is its potential to address additional important questions regarding epidemiology and spina bifida. The classification of spinal defects is complex, and this study adds to the limited distribution data that exist for prefortification and postfortification subtypes. | | The study concluded that the overall prevalence of severe upper-level lesions in spina bifida cases experienced a steep reduction following mandatory folic acid fortification institution within the United States, whereas no change in the prevalence of less severe lower-level lesions took place. Additional examinations are warranted to better understand the magnitude and mechanism of spina bifida severity in relation to folic acid intake. |
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