Background:Malaria is a mosquito borne disease caused by parasites of the genus Plasmodium. In 2023, the United States (US) experienced nine cases of autochthonous Plasmodium vivax malaria transmission; seven in Florida, one in Texas, and another in Arkansas. These were the first autochthonous cases since 2003 when a cluster was identified in Florida. The aim of this study was to genetically characterize the implicated P. vivax isolates in order to complement epidemiologic investigations of these cases. Methods:A custom Illumina AmpliSeq sequencing panel capturing 495 amplicons was designed. This panel was used to ascertain whether these 2023 cases were related, and assess if they were associated with a single or separate introduction events. Sequence data were hierarchically clustered and a Naïve Bayes classification approach was used to assign genotypes to a probable geographic origin based on 113 'geo-informative' SNPs captured by the panel. Genotypes associated with the 2023 Arkansas, Texas, and Florida cases were clustered alongside those sequenced from archived blood samples from the 2003 Florida case-patients, a set of reference strains, and other travel-associated specimens. Microsatellite analysis was performed on a subset of samples from these autochthonous cases to complement the AmpliSeq analysis. Findings:The 2023 autochthonous Florida cases were genetically linked as were the 2003 Florida cases. The 2023 and 2003 Florida clusters were genetically distinct, and the two Florida clusters were distinct from the 2023 Texas and Arkansas cases, which were also distinct from each other. These genotypes classified to the Central or South American region using the Naïve Bayes classifier, including those from the 2003 cluster. Interpretation:These data support that at least three distinct P. vivax introduction events in the US in 2023, involving parasites possessing genetic signatures consistent with Central or South America. Funding:This work was supported by the National Center for Emerging and Zoonotic Infectious Diseases at the US Centers for Disease Control and Prevention.

Abstract Background Between 200–300 severe malaria cases are diagnosed annually in the U.S. Intravenous artesunate (IVAS), the FDA-approved 1st-line therapy for severe malaria since 2020, is commercially available but at high cost. Uncertainty regarding where people with severe malaria will seek medical care poses supply chain challenges. We identified hospitals where people with severe malaria were treated and mapped proximity to Level 1 trauma centers as a proxy for hospitals that provide complex clinical care, which could assist with planning for IVAS distribution. Location identification and manual adjudication process for hospitals that hospitalized people with severe malaria as reported to CDC from 2012–2018. Of the original 1,912 cases of severe malaria reported to the CDC from 2012-2018, we excluded 379 cases that were not admitted or were admitted but missing a hospital name. Of the remaining 1,533 severe malaria cases that were eligible for adjudication, 1,237 were an exact match with an existing hospital location. Of the 296 cases that were not an exact match, we manually adjudicated 229 cases by clarifying a hospital name that was abbreviated, incomplete, or had a change in name; only 49 cases could not be identified given multiple possible sites with the same name, and 18 cases with no name that matched a hospital site. Six additional cases were excluded because of occurring at a site with no Level 1 trauma center within driving distance (i.e., Alaska and US Virgin Islands). Methods Using 2012–2018 data reported to the Centers for Disease Control and Prevention (CDC), we analyzed free text of U.S. hospital names where people were treated as inpatients for severe malaria. We identified these hospitals using Google Maps Geocoding Application Programming Interface (API) followed by manual adjudication. We excluded cases when data were incomplete or ambiguous or if a Level 1 trauma center was inaccessible (e.g., Alaska or U.S. Virgin Islands). We then mapped hospitals to U.S. counties and estimated travel times between hospitals and the nearest Level 1 trauma center as per 2014–2016, using Google Maps Distance Matrix API. Average numbers of severe malaria cases at identified hospitals per US county annually as reported to the CDC during 2012–2018. Panel A shows the geographic distribution and average number of severe malaria cases at identified hospitals per year by county reported to CDC during 2012–2018; darker color shows counties with more severe malaria cases reported. Panel B shows that the distribution is highly skewed to 2 counties that reported more than 10 inpatient cases annually; 2,824 counties (pale peach) reported no cases of severe malaria admitted to an identified hospital during 2012–2018. Results After excluding 379 cases with no recorded hospital name from 1,912 severe malaria cases, we successfully adjudicated hospitals for 1,460/1,533 cases (Fig 1). Two counties reported >10 inpatient cases per year (Bronx County, NY and New York County, NY), and 2,824 counties never reported a hospitalized severe malaria case (Fig 2). Almost 35% of inpatient cases occurred at Level 1 trauma centers (508/1,460 [34.8%]) (Fig 3). Of the 952/1,460 (65.2%) inpatient cases not at Level 1 trauma centers, 891/952 (93.5%) were at hospitals located < 2h estimated driving time of a Level 1 trauma center. Only 61/1,460 (4.2%) cases were at locations >2h from a Level 1 trauma center. Limitations include that the analysis did not consider the original site of clinical presentation with malaria or locations of people with severe malaria not hospitalized. Histogram of modeled travel times between each severe malaria case at an identified hospital and the nearest Level 1 trauma center. Of severe malaria cases reported to CDC in 2012–2018 and hospitalized at an identified hospital, 34.8% were treated at Level 1 trauma centers (red bar); for severe malaria cases that were not at Level 1 trauma centers, we found that modeled transit times between treatment site and Level 1 trauma center were less than 2 hours except in 4.2% of severe malaria cases at an identified hospital (right of black dashed vertical line). Conclusion More than 95% of people admitted for severe malaria at identified hospitals reported to the CDC in 2012–2018 were at or within 2h estimated driving time of a Level 1 trauma center, which may suggest priorities for implementing IVAS distribution. Disclosures Alison Ridpath, MD, MPH, Abbvie Inc.: Stocks/Bonds (Public Company)|Amarin Corperation PLC: Stocks/Bonds (Public Company)|Amgen Inc: Stocks/Bonds (Public Company)|BioNTech: Stocks/Bonds (Public Company)|Immunic Inc: Stocks/Bonds (Public Company)|infinity Pharmaceutical Companies: Stocks/Bonds (Public Company)|IQVIA Holdings Inc: Stocks/Bonds (Public Company)|Johnson and Johnson: Stocks/Bonds (Public Company)|Merck and Co inc: Stocks/Bonds (Public Company)|Pfizer Inc.: Stocks/Bonds (Public Company)|Protagonist Therapeutics: Stocks/Bonds (Public Company)

A case of locally acquired (autochthonous) mosquito-transmitted Plasmodium vivax malaria was diagnosed in Arkansas in September 2023. This represents the 10th autochthonous case identified nationally in 2023, after 20 years without recorded local mosquitoborne malaria transmission in the United States. The public health response included case investigation, active case surveillance, mosquito surveillance and control, assessment of medical countermeasures, and clinical and public outreach. Prompt diagnosis and appropriate treatment of malaria can improve clinical outcomes and, in addition to vector control, minimize risk for local transmission. Clinicians should consider malaria among patients who have traveled to countries where malaria is endemic, or with unexplained fever regardless of travel history. Although the risk for autochthonous malaria in the United States remains very low, its reemergence highlights the importance of vectorborne disease preparedness and response. Examples of such efforts include improving awareness among clinicians, access to diagnostics and antimalarial medications, and capacity for mosquito surveillance and control. Collaboration and communication among CDC, health departments, local jurisdictions, clinicians, hospitals, laboratories, and the public can support rapid malaria diagnosis, prevention, and control. Before traveling internationally to areas where malaria is endemic, travelers should consult with their health care provider regarding recommended malaria prevention measures, including chemoprophylaxis and precautions to avoid mosquito bites, to reduce both personal and community risk.

Malaria is a serious and potentially fatal disease transmitted through the bite of an infective female anopheline mosquito; pregnant people are more susceptible to malaria infection than nonpregnant people, and are at risk of significant adverse consequences for both mother and infant. 1 These include maternal anemia, fetal growth retardation, stillbirth, premature birth, and low birthweight. 2Rarely, malaria can be transmitted congenitally from mother to fetus or to the neonate at birth.Globally, it is estimated that over 13 million pregnancies were affected by malaria in 2021, leading to an estimated 505,000 infants born with low birth weight. 3 While malaria in pregnancy is rarely seen in the United States, it nonetheless occurs, with 19 cases among pregnant women (both travelers and refugees/immigrants) reported in the US in 2018, 4 27 in 2019 (Mace, unpublished data), and 8 in 2020 (Mace, unpublished data), and needs to be recognized and treated quickly to prevent adverse effects to the mother and infant.Until recently, only chloroquine, mefloquine, or quinine plus clindamycin were recommended for treatment of uncomplicated malaria in the first trimester.Artemether-lumefantrine (Coartem®) was approved in the United States in 2009 for the treatment of uncomplicated malaria in non-pregnant individuals; due to limited data, the FDA classified it as class C, indicating that use in pregnancy should be reserved for situations in which the benefit outweighed possible risks.With increasing data demonstrating the safety of ACTs in 2 nd and 3 rd

This paper discusses challenges in formulating and harmonizing malaria prevention recommendations for travellers. It explores diverse approaches used by advisory groups to assess malaria risk and shares insights from the 2023 International Expert Committee for Travel Medicine meeting. It also explores future prospects for enhancing malaria prevention recommendations for travellers.

Eight cases of locally acquired, mosquito-transmitted (i.e., autochthonous) Plasmodium vivax malaria, which has not been reported in the United States since 2003, were reported to CDC from state health departments in Florida and Texas during May 18-July 17, 2023. As of August 4, 2023, case surveillance, mosquito surveillance and control activities, and public outreach and education activities continue in both states. U.S. clinicians need to consider a malaria diagnosis in patients with unexplained fever, especially in areas where autochthonous malaria has been recently reported, although the risk for autochthonous malaria in the United States remains very low. Prompt diagnosis and treatment of malaria can prevent severe disease or death and limit ongoing transmission to local Anopheles mosquitoes and other persons. Preventing mosquito bites and controlling mosquitoes at home can prevent mosquitoborne diseases, including malaria. Before traveling internationally to areas with endemic malaria, travelers should consult with a health care provider regarding recommended malaria prevention measures, including potentially taking malaria prophylaxis. Malaria is a nationally notifiable disease; continued reporting of malaria cases to jurisdictional health departments and CDC will also help ensure robust surveillance to detect and prevent autochthonous malaria in the United States.

BackgroundChancroid has been a nationally notifiable condition in the United States since 1944, with cases reported to Centers Disease Control and Prevention through the National Notifiable Diseases Surveillance System. Although frequently reported during the 1940s, MethodsWe reviewed the literature to contextualize chancroid surveillance through National Notifiable Diseases Surveillance System. We then assessed 4 system attributes, including data quality, sensitivity, usefulness, and representativeness: we reviewed chancroid cases reported during 2011-2020, conducted interviews with (a) sexually transmitted disease programs reporting & GE;1 case in 2019 or 2020 (n = 9) and (b) Centers Disease Control and Prevention subject matter experts (n = 10), and reviewed published communicable disease reporting laws.ResultsChancroid diagnostic testing is limited, which affects the surveillance case definition. National case-based surveillance has poor data quality; of the 2019 and preliminary 2020 cases (n = 14), only 3 were verified by jurisdictions as chancroid cases. Sexually transmitted disease programs report the system has low sensitivity given limited clinician knowledge and resources; experts report the system is not useful in guiding national control efforts. Review of reporting laws revealed it is not representative, as chancroid is not a reportable condition nationwide.ConclusionsCritical review of system attributes suggest that national case-based chancroid surveillance data have limited ability to help describe and monitor national trends, and chancroid's inclusion on the national notifiable list might need to be reconsidered. Alternative strategies might be needed to monitor national chancroid burden.

Background Nonviral sexually transmitted infections (STIs) increase risk of sexually acquired human immunodeficiency virus (HIV) infection. Updated risk estimates carefully scrutinizing temporality bias of studies are needed. Methods We conducted a systematic review (PROSPERO CRD42018084299) of peer-reviewed studies evaluating variation in risk of HIV infection among high-risk heterosexuals diagnosed with any of: Chlamydia trachomatis, Mycoplasma genitalium, Neisseria gonorrhoeae, Treponema pallidum, and/or Trichomonas vaginalis. We searched PubMed, Web of Science, and Embase databases through December 2017 and included studies where STIs and HIV were assessed using laboratory tests or medical examinations and where STI was diagnosed before HIV. After dual screening, data extraction, and risk of bias assessment, we meta-analytically pooled risk ratios (RRs). Results We found 32 eligible studies reporting k = 97 effect size estimates of HIV acquisition risk due to infection with one of the abovementioned STIs. Most data were based on women engaged in sex work or other high-risk occupations in developing countries. Many studies did not measure or adjust for known confounders, including drug injection and condom use, and most were at medium or high risk of bias because of the potential for undetected HIV infection to have occurred before STI infection. Human immunodeficiency virus acquisition risk increased among women infected with any pathogen; the effect was greatest for women infected with Mycoplasma genitalium (RR, 3.10; 95% confidence interval [CI], 1.63-5.92; k = 2) and gonorrhea (RR, 2.81; 95% CI, 2.25-3.50; k = 16) but also statistically significant for women infected with syphilis (RR, 1.67; 95% CI, 1.23-2.27; k = 17), trichomonas (RR, 1.54; 95% CI, 1.31-1.82; k = 17), and chlamydia (RR, 1.49; 95% CI, 1.08-2.04; k = 14). For men, data were space except for syphilis (RR, 1.77; 95% CI, 1.22-2.58; k = 5). Conclusion Nonviral STI increases risk of heterosexual HIV acquisition, although uncertainty remains because of risk of bias in primary studies.

Background Shigella species, which cause acute diarrheal disease, are transmitted via fecal-oral and sexual contact. To better understand the overlapping populations affected by Shigella infections and sexually transmitted infections (STIs) in the United States, we examined the occurrence of reported STIs within 24 months among shigellosis case-patients. Methods Culture-confirmed Shigella cases diagnosed from 2007 to 2016 among residents of 6 US jurisdictions were matched to reports of STIs (chlamydia, gonorrhea, and all stages of syphilis) diagnosed 12 months before or after the shigellosis case. We examined epidemiologic characteristics and reported temporal trends of Shigella cases by sex and species. Results From 2007 to 2016, 10,430 shigellosis cases were reported. The annual number of reported shigellosis cases across jurisdictions increased 70%, from 821 cases in 2007 to 1398 cases in 2016; males saw a larger increase compared with females. Twenty percent of male shigellosis case-patients had an STI reported in the reference period versus 4% of female case-patients. The percentage of male shigellosis case-patients with an STI increased from 11% (2007) to 28% (2016); the overall percentage among females remained low. Conclusions We highlight the substantial proportion of males with shigellosis who were diagnosed with STIs within 24 months and the benefit of matching data across programs. Sexually transmitted infection screening may be warranted for male shigellosis case-patients.

Abstract Background Disseminated gonococcal infections (DGI) are estimated to occur in 0.5% to 3% of untreated Neisseria gonorrhoeae (GC) infections; however, surveillance and population-based studies to estimate DGI burden and describe recent DGI epidemiology and clinical manifestations are limited. In response to increased reports of DGI cases and clusters in the U.S., the Centers for Disease Control and Prevention (CDC) developed a surveillance system in 2020. We analyzed data captured by the initial two years of surveillance. Methods During 1/1/2020–3/31/2022, U.S. state/local health jurisdictions reported DGI cases to CDC utilizing a standardized case report form that collects demographic, sociobehavioral, and clinical information. A confirmed case was defined as isolation or detection of GC from a disseminated site of infection by culture or nucleic acid amplification test (NAAT); a probable case was defined as clinical manifestations of DGI and isolation or detection of GC from a mucosal site by culture or NAAT. Results In total, 274 DGI cases were reported to CDC from 13 U.S. states (65.7% from California): 215 (78.5%) confirmed cases and 59 (21.5%) probable cases. Among DGI cases, 51.1% were cisgender male, 33.2% were ≥ 45 years old, and 26.6% reported methamphetamine use in the past 12 months. Most patients (87.6%) did not have documented underlying immunosuppression or predisposing medical conditions. Among patients with DGI, 85.8% were hospitalized, 41.2% underwent related surgeries, and 2.2% died. Among confirmed cases, the most common disseminated sites of infection were synovial fluid (50.2%) and blood (45.1%). Among 184 (67.2%) patients with DGI who were tested for GC at a mucosal site, 115 (62.5%) were diagnosed with a mucosal GC infection (69.6% urogenital, 27.0% pharyngeal, 12.2% rectal); however, 85.5% of those not diagnosed with mucosal GC were only tested at urogenital sites. Only 89 patients (32.5%) reported mucosal symptoms present at the time of or within the month prior to DGI presentation. Conclusion Health care providers should maintain a high degree of suspicion for patients presenting with DGI symptoms given the potential for significant associated morbidity and the low proportion of patients who present with concurrent GC mucosal symptoms. Disclosures Alison Ridpath, MD, MPH, 3M company: Stocks/Bonds|Abbott Laboratories: Stocks/Bonds|Abbvie Inc.: Stocks/Bonds|Allogene Theraputics: Stocks/Bonds|Amarin Corperation PLC: Stocks/Bonds|infinity Pharmaceutical Companies: Stocks/Bonds|IQVIA Holdings Inc: Stocks/Bonds|Johnson and Johnson: Stocks/Bonds|Medtronic: Stocks/Bonds|pfizer: Stocks/Bonds|Thermo Fisher Scientific: Stocks/Bonds.

BackgroundMen who have sex with men (MSM) who have bacterial sexually transmitted infections (STIs) are at increased risk for HIV infection. We enhanced and updated past summary risk estimates.MethodsWe systematically reviewed (PROSPERO No. CRD42018084299) peer-reviewed studies assessing the risk of HIV infection among MSM attributable to Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and/or Trichomonas vaginalis (TV). We searched 3 databases through December 2017. We excluded studies with self-reported data or simultaneous STI and HIV assessment. We conducted dual screening and data extraction, meta-analytically pooled risk ratios (RRs), and assessed potential risk of bias.ResultsWe included 26 studies yielding 39 RR (k) for HIV acquisition due to one of TP, NG, or CT. We did not identify eligible data for MG or TV, or for HIV transmission. HIV acquisition risk increased among MSM infected with TP (k = 21; RR, 2.68, 95% confidence interval [CI], 2.00-3.58), NG (k = 11; RR, 2.38; 95% CI, 1.56-3.61), and CT (k = 7; RR, 1.99; 95% CI, 1.59-2.48). Subanalysis RRs for all 3 pathogens were >= 1.66 and remained statistically significant across geography and methodological characteristics. Pooled RR increased for data with the lowest risk of bias for NG (k = 3; RR, 5.49; 95% CI, 1.11-27.05) and TP (k = 4; RR, 4.32; 95% CI, 2.20-8.51). We observed mostly moderate to high heterogeneity and moderate to high risk of bias.ConclusionsMen who have sex with men infected with TP, NG, or CT have twice or greater risk of HIV acquisition, although uncertainties exist because of data heterogeneity and risk of bias.

Background Responding effectively to outbreaks of antibiotic-resistant gonorrhea (ARGC) in the future will likely prove challenging. Tabletop exercises (TTXs) may assist local, state, and federal public health officials evaluate existing ARGC outbreak response plans, strengthen preparedness and response effectiveness, and identify critical gaps to address before an outbreak. Methods In 2018 to 2019, Centers for Disease Control and Prevention (CDC) collaborated with state partners to develop and implement TTXs to simulate a public health emergency involving an ARGC outbreak. Before the TTXs, 2 state-local health department pairs developed ARGC outbreak response plans. During each 1-day exercise (in Indiana and Illinois), participants discussed roles, clinical management, public health response, and communication based on predeveloped response plans. Observers identified outbreak response strengths and gaps, and participants completed feedback forms. Results Forty-one (Illinois) and 48 people (Indiana) participated in each TTX, including sexually transmitted disease clinical staff, laboratorians, public health infectious disease program staff, and CDC observers. Strengths and gaps varied by jurisdiction, but identified gaps included: (1) local access to gonorrhea culture and timely antimicrobial susceptibility testing, (2) protocols for clinical management of suspected treatment failures, (3) communication plans, and (4) clarity regarding state and local responsibilities. The CDC observers identified opportunities to provide national-level technical assistance, foster local antimicrobial susceptibility testing, and develop further response guidance. Tabletop exercises summary reports were used to guide modifications to local response plans to address gaps. Conclusions The TTXs allowed participants to practice responding to a simulated public health emergency and may have enhanced local response capacity. Centers for Disease Control and Prevention made TTX implementation materials publicly available.

INTRODUCTION:In January 2019, the West Virginia Bureau for Public Health detected increased HIV diagnoses among people who inject drugs in Cabell County. Responding to HIV clusters and outbreaks is 1 of the 4 pillars of the Ending the HIV Epidemic in the U.S. initiative and requires activities from the Diagnose, Treat, and Prevent pillars. This article describes the design and implementation of a comprehensive response, featuring interventions from all pillars. METHODS:This study used West Virginia Bureau for Public Health data to identify HIV diagnoses during January 1, 2018-October 9, 2019 among (1) people who inject drugs linked to Cabell County, (2) their sex or injecting partners, or (3) others with an HIV sequence linked to Cabell County people who inject drugs. Surveillance data, including HIV-1 polymerase sequences, were analyzed to estimate the transmission rate and timing of infections using molecular clock phylogenetic analysis. Federal, state, and local partners designed and implemented a comprehensive response during January 2019-October 2019. RESULTS:Of 82 people identified in the outbreak, most were male (60%), were White (91%), and reported unstable housing (80%). In a large molecular cluster containing 56 of 60 (93%) available sequences, 93% of inferred transmissions occurred after January 1, 2018. HIV testing, HIV pre-exposure prophylaxis, and syringe services were rapidly expanded, leading to improved linkage to HIV care and viral suppression. CONCLUSIONS:Evidence of rapid transmission in this outbreak galvanized robust collaboration among federal, state, and local partners, leading to critical improvements in HIV prevention and care services. HIV outbreak response requires increased coordination and creativity to improve service delivery to people affected by rapid HIV transmission.

Quilter, Laura A. S. MD, MPH; Agnew-Brune, Christine PhD, MPH; Broussard, Dawn MPH; Salmon, Melinda BA; Bradley, Heather PhD; Hogan, Vicki MPH; Ridpath, Alison MD, MPH; Burton, Kenya PhD, MA, MS; Rose, Bridget Connard BA; Kirk, Nathan BA; Reynolds, Pamela BA; Varella, Lisa BS; Granado, Michael MPA; Gerard, Anthony BS; Thompson, Antoine MPA; De La Garza, Gloria BA; Lee, Chang BA; Bernstein, Kyle PhD, ScMAuthor Information

A recent human immunodeficiency virus (HIV) outbreak among people who inject drugs in Cabell County, West Virginia, underscores the importance of HIV prevention, diagnosis, and care in communities with high rates of substance use disorder.