Metagenomic Nanopore Sequencing of Tickborne Pathogens, Mongolia
We performed nanopore-based metagenomic screening on 885 ticks collected from 6 locations in Mongolia and divided the results into 68 samples: 23 individual samples and 45 pools of 2-12 tick samples each. We detected bacterial and parasitic pathogens Anaplasma ovis, Babesia microti, Coxiella burnetii, Borrelia miyamotoi, Francisella tularensis subsp. holarctica and novicida, Spiroplasma ixodetis, Theileria equi, and Rickettsia spp., including R. raoultii, R. slovaca, and R. canadensis. We identified the viral pathogens Crimean-Congo hemorrhagic fever virus (2.9%), recently described Alongshan virus (ALSV) (2.9%), and Beiji nairovirus (5.8%). We assembled ALSV genomes, and maximum-likelihood analyses revealed clustering with viruses reported in humans and ticks from China. For ALSV, we identified surface glycoprotein markers associated with isolates from Asia viruses hosted by Ixodes persulcatus ticks. We also detected 20 virus species of unknown public health impact, including a near-complete Yanggou tick virus genome. Our findings demonstrate that nanopore sequencing can aid in detecting endemic and emerging tickborne pathogens.
Incursion of Novel Eurasian Low Pathogenicity Avian Influenza H5 Virus, Australia, 2023
Australia is a sink for low pathogenicity avian influenza viruses, with isolated circulation occurring on the continent. We report the incursion of a Eurasian low pathogenicity avian influenza H5 virus into Australia. This report benefits surveillance and diagnostic work because of the risk and current absence of highly pathogenic avian influenza A(H5N1).
Fatal Mixed Plasmodium Infection in Traveler Returning to Colombia from Comoros Islands, 2024
During 2014-2022, only Plasmodium falciparum malaria cases were reported in the Comoro Islands. We report a fatal case of mixed Plasmodium malaria infection in a traveler returning from the Comoros to Colombia in 2024, highlighting the need to strengthen laboratory detection and identification of Plasmodium spp. in sub-Saharan Africa.
Heartland Virus Infection in Elderly Patient Initially Suspected of Having Ehrlichiosis, North Carolina, USA
We report a patient in North Carolina, USA, with Heartland virus infection whose diagnosis was complicated by previous Ehrlichia chaffeensis infection. We identified E. ewingii-infected and Bourbon virus-infected tick pools at the patient's residence. Healthcare providers should consider testing for tickborne viruses if ehrlichiosis is suspected.
Comprehensive Surveillance of Severe Fever with Thrombocytopenia Syndrome Virus in Patients with Acute Febrile Illness, Wild Rodents, and Trombiculid Larval Mites, Thailand
Infection with severe fever with thrombocytopenia syndrome (Bandavirus dabieense) virus poses a substantial public health threat because of its high mortality rates and severe complications. The virus is prevalent in Asia, although data from Thailand are scarce. Our study confirmed the virus in 1.6% of acute febrile illness patients and specific antibodies in 3% of archived samples since 2015 in Thailand. Nationwide zoonotic surveillance identified the virus in 8 rodent species and 4 chigger genera. Our findings underscore the importance of raising awareness among healthcare providers and the general public about the symptoms, risks, and prevention strategies associated with severe fever with thrombocytopenia syndrome virus infection. Ongoing surveillance of the virus in human and animal populations is essential for monitoring its prevalence, distribution, and potential for emergence.
Global Emerging Infections Surveillance Program Contributions to Pandemic Preparedness and Response
Since its establishment in 1997, the US Department of Defense (DoD) Global Emerging Infections Surveillance (GEIS) program has provided support for infectious disease pandemic preparedness and response. The GEIS program has shown the value of having a central hub responsible for coordinating a global network of DoD laboratories that conduct surveillance for militarily relevant infectious disease threats. The program has supported the establishment and maintenance of capabilities for collecting, characterizing, and reporting on major infectious disease events, including the COVID-19 pandemic and mpox outbreak. The GEIS program enables the US government to mitigate infectious disease threats to DoD mission readiness and to effectively respond to pathogens worldwide. Continued investment in maintaining the GEIS program and its network is critical for timely detection and response to future emerging infectious disease threats in various populations within locations where gaps in US government or host-nation surveillance might exist.
Scrub Typhus Outbreak among Soldiers in Coastal Training Area, Australia, 2022
A scrub typhus outbreak occurred among 24 soldiers from 2 Australian Defence Force infantry units following separate training events conducted in the same coastal location in tropical North Queensland, Australia, in June 2022. Seven soldiers visited a hospital, 5 requiring admission. Outbreak recognition was hampered by the geographic dispersion of soldiers after the exercise and delayed case identification resulting from such factors as prolonged incubation, cross-reactive serologic responses to other pathogens, the nonspecific symptoms of scrub typhus, and the illness's nonnotifiable status in the state of Queensland. Our investigation focused on personal protective measures in a subanalysis of 41 soldiers, revealing an association between scrub typhus infection and the use of doxycycline chemoprophylaxis and permethrin uniform dipping.
Respiratory Disease Surveillance in the Middle East and Latin America during the COVID-19 Pandemic, 2020-2022
Characterizing the epidemiology of circulating respiratory pathogens during the COVID-19 pandemic could clarify the burden of acute respiratory infections and monitor outbreaks of public health and military relevance. The US Department of Defense supported 2 regions for influenza-like illness and severe acute respiratory infections surveillance, one in the Middle East through US Naval Medical Research Unit EURAFCENT, and another in Latin America through US Naval Medical Research Unit SOUTH. During 2020‒2022, coinciding with the COVID-19 pandemic, we collected a total of 16,146 nasopharyngeal and oropharyngeal swab samples from sentinel sites in Jordan (n = 11,305) and Latin America (n = 4,841). Samples were tested for SARS-CoV-2, influenza, and other respiratory pathogens. SARS-CoV-2 was the most frequently detected pathogen during 2020; other respiratory pathogens had distinct temporal and frequency distributions according to geographic location. Our findings support the need for continued sentinel surveillance as a vital tool for assessing the burden of respiratory diseases globally.
Highly Pathogenic Avian Influenza A(H5N1) Virus Infection in Cats, South Korea, 2023
In July 2023, cases of highly pathogenic avian influenza (HPAI) were reported at 2 shelters for stray cats in Seoul, South Korea. The cause of infection was suspected to be improperly sterilized raw food made from domestic duck meat, which was manufactured in South Korea. All viruses isolated from cats at the shelters and from the raw food belonged to HPAI A(H5N1) clade 2.3.4.4b. The gene constellation of all viruses was most similar to that of viruses isolated in Korea in November 2022. Of note, the viruses isolated from infected cats harbored mutations E627K or D701N in polymerase basic 2, which are indicative of adaptation to mammals. Postmortem examination revealed systemic pathologic lesions and the presence of widespread virus in different tissues. Thus, consumption of raw duck meat contaminated with HPAI virus likely caused systemic symptoms and death in cats, indicating the introduction of mammal-adapted mutations of the virus.
The Central Role of the Global Emerging Infections Surveillance Program in Supporting Force Health Protection
The Global Emerging Infections Surveillance (GEIS) program is the only Department of Defense (DoD) organization that coordinates global surveillance for emerging infectious diseases that affect US military forces operating in the United States or foreign locations. Since 1997, the GEIS program has focused on surveilling pathogens likely to affect military operations and the health of service members. The foundation of the GEIS program is the long-standing, mutually beneficial relationships between the DoD overseas laboratories and their host-country partners and militaries. Through centralized programmatic support, the GEIS program provides the infrastructure needed for a rapid and scalable response to emerging threats. The GEIS program continues to enhance and evolve its initiatives to provide timely, reliable information to decision-makers in the DoD. The GEIS program has been and will continue to be a vital source of actionable biosurveillance information during infectious disease events of global public health concern.
Next-Generation Sequencing and Bioinformatics Consortium Approach to Genomic Surveillance
Genomic surveillance programs benefit greatly from a network of committed, well-supported laboratories that conduct ongoing surveillance activities for pathogens of public health importance. The experiences of the Global Emerging Infections Surveillance program provide insights for building and maintaining genomic surveillance capabilities for public health and pandemic preparedness and response. To meet the needs of US Department of Defense and the Military Health System to use genomics to monitor pathogens of military and public health importance, Global Emerging Infections Surveillance convened a consortium of experts in genome sequencing, bioinformatics, and genomic epidemiology. The experts developed a 3-tiered framework for building and maintaining next-generation sequencing and bioinformatics capabilities for genomic surveillance within the Department of Defense. The consortium strategy was developed before the COVID-19 pandemic, leading to a network prepared to respond with existing resources and expand as new funding became available.
Redesigning Surveillance through the Global Emerging Infections Surveillance Program
Molecular Characterization of Noroviruses Causing Acute Gastroenteritis Outbreaks among US Military Recruits, 2013-2023
Norovirus is the leading cause of acute gastroenteritis (AGE) worldwide. Norovirus outbreaks at military facilities can cause loss of training and working days and increased healthcare utilization, affecting force readiness. During 2013-2023, we enrolled 2,304 US military recruits from 4 basic training facilities to investigate AGE outbreaks among this population. Among enrollees, we detected norovirus in 433 (18.8%) AGE cases, and norovirus caused 49 AGE outbreaks during our longitudinal study. On average, each norovirus case-patient missed 1.2 training days due to illness, and 6.2% required infusion care. Whole-genome sequencing of selected samples from each outbreak produced full-length genomes (6,989-7,787 bp) for 39 samples. Norovirus GII.4 Sydney was the most (12/39, 30.8%) identified genotype over the study period. Phylogenetic and comparative genomic analyses revealed that several outbreak strains were responsible for causing >1 outbreak, even across different training sites. Our findings can inform infection control practices at military installations and overall norovirus vaccine development.
Molecular Surveillance of Multidrug-Resistant Bacteria among Refugees from Afghanistan in 2 US Military Hospitals during Operation Allies Refuge, 2021
In 2021, two US military hospitals, Landstuhl Regional Medical Center in Landstuhl, Germany, and Walter Reed National Military Medical Center (WRNMMC) in Bethesda, Maryland, USA, observed a high prevalence of multidrug-resistant bacteria among refugees evacuated from Afghanistan during Operation Allies Refuge. Multidrug-resistant isolates collected from 80 patients carried an array of antimicrobial resistance genes, including carbapenemases (bla, bla, and bla) and 16S methyltransferases (rmtC and rmtF). Considering the rising transmission of antimicrobial resistance and unprecedented population displacement globally, these data are a reminder of the need for robust infection control measures and surveillance.
Common Patterns and Unique Threats in Antimicrobial Resistance as Demonstrated by Global Gonococcal Surveillance
The rapid emergence of antimicrobial-resistant strains of Neisseria gonorrhoeae threatens treatment options and control efforts. The Uniformed Services University Gonococcal Reference Laboratory and Repository of the Global Emerging Infections Surveillance Program receives isolates from several geographically distinct regions worldwide. We analyzed 962 isolates collected during 2014-2022 for genomic and phenotypic antimicrobial resistance. Resistance to antimicrobial drugs previously used for gonococcal infections was high, but of most concern were increases of resistance to currently used antibiotic drugs, such as extended-spectrum cephalosporins and the alternative antibiotic treatment gentamicin. The percentage of isolates with reduced susceptibility to ceftriaxone was 3.6%, to cefixime was 2.5%, and to gentamicin was 15.0%. Although isolates were collected from populations of limited diversity, 706 (73.4%) of isolates demonstrated novel multiantigen sequence types, and 225 (23.4%) had novel multilocus sequence types. Continued surveillance of N. gonorrhoeae is essential to monitoring the prevalence and spread of resistant organisms worldwide.
Serosurveillance for Plasmodium falciparum Malaria in Peruvian Army Peacekeeping Personnel, Central African Republic, 2021-2022
Plasmodium falciparum infection threatens military populations deployed to highly malaria-endemic regions, such as Peruvian Army peacekeepers deployed to Central African Republic. During deployment, malaria cases were identified by microscopy and rapid diagnostic tests. After deployment, we performed malaria diagnosis by malachite green loop-mediated isothermal amplification and photo-induced electron transfer PCR assays. We used ELISA to test for P. falciparum C-terminal 19-kDa region merozoite surface protein 1-specific IgG from 97 peacekeepers. Malaria prevalence during deployment was 33.33% and we detected 4 cases after deployment: P. falciparum (n = 2), P. ovale (n = 1), and Plasmodium spp. (n = 1). IgG surveillance showed a seroprevalence of 31.96% in peacekeepers, who had a high P. falciparum exposure during deployment. Our findings reinforce the necessity of active surveillance in military populations to reduce the risk for introduction of new Plasmodium species and strains into the Americas from malaria-endemic areas.
Azithromycin Resistance Patterns in Escherichia coli and Shigella before and after COVID-19, Kenya
Escherichia coli and Shigella spp. are leading bacterial causes of acute diarrhea in sub-Saharan Africa and pose risks to global communities, travelers, and the US military. Increasing antimicrobial resistance (AMR) in those and other enteric pathogens creates treatment challenges for clinicians. Inappropriate use of antimicrobial drugs, such as azithromycin for viral respiratory infections, increased during the COVID-19 pandemic. We evaluated AMR trends of 116 E. coli and 109 Shigella spp. isolates obtained from 1,672 pre-COVID-19 (2017-2019) and 1,118 post-COVID-19 (2022-2023) human fecal samples from Kenya. Azithromycin resistance increased significantly from before to after COVID-19, from 6.3% to 40.4% (p = 0.001). Phenotypic AMR profiles from a subset of isolates were compared with genotypic AMR information derived from whole genome sequencing. The most common AMR gene detected was the macrolide mph(A) gene. This study highlights the need for continued AMR surveillance.
Genomic Epidemiology of Multidrug-Resistant Escherichia coli and Klebsiella pneumoniae in Kenya, Uganda, and Jordan
Surveillance of antimicrobial resistance in Kenya, Uganda, and Jordan identified multidrug-resistant high-risk bacterial clones: Escherichia coli sequence types 131, 1193, 69, 167, 10, 648, 410, 405 and Klebsiella pneumoniae sequence types 14, 147, 307, 258. Clones emerging in those countries exhibited high resistance mechanism diversity, highlighting a serious threat for multidrug resistance.
Etiology and Epidemiology of Travelers' Diarrhea among US Military and Adult Travelers, 2018-2023
Travelers' diarrhea has a high incidence rate among deployed US military personnel and can hinder operational readiness. The Global Travelers' Diarrhea study is a US Department of Defense--funded multisite surveillance effort to investigate the etiology and epidemiology of travelers' diarrhea. During 2018-2023, we enrolled 512 participants at partner institutions in 6 countries: Djibouti, Georgia, Egypt, Honduras, Nepal, and Peru. Harmonized laboratory methods conducted at each partner institution identified >1 pathogens, including Escherichia coli (67%-82%), norovirus (4%-29%), and Campylobacter jejuni (2%-20%), in 403 (79%) cases. Among cases, 79.7% were single infections, 19.6% were double infections, and 0.7% were triple infections. The most common enterotoxigenic E. coli colonization factors identified were CS3 (25%) and CS21 (25%), followed by CS2 (18%) and CS6 (15%). These data can inform best treatment practices for travelers' diarrhea and support US military health readiness.
Using SARS-CoV-2 Sequencing Data to Identify Reinfection Cases in the Global Emerging Infections Surveillance Program, United States
The Centers for Disease Control and Prevention defines SARS-CoV-2 reinfection as a positive COVID-19 test result >90 days after the collection date for the initial positive test or if sequencing confirms a different lineage is causing the reinfection. Reinfection dynamics have been examined by using PCR or antigen surveillance data. We identified patients in the US Military Health System who had >1 positive SARS-CoV-2 test during March 2020-July 2022 by using whole-genome sequencing data to identify reinfection cases, then compared those data with patient demographics, symptoms, and vaccination status. We identified 267 reinfections, of which 90% were caused by the SARS-CoV-2 Omicron variant. Reinfection symptom severity correlated with initial symptom severity and time since first infection. Furthermore, we found intrahost mutation rates varied greatly in 72 cases of continuing infections with the same variant. Continued investigations of reinfections caused by emerging SARS-CoV-2 variants of concern is needed to maintain US military readiness.
Characteristics of Madariaga and Venezuelan Equine Encephalitis Virus Infections, Panama
Madariaga virus (MADV) and Venezuelan equine encephalitis virus (VEEV) are emerging arboviruses affecting rural and remote areas of Latin America. However, clinical and epidemiologic reports are limited, and outbreaks are occurring at an increasing frequency. We addressed the data gap by analyzing all available clinical and epidemiologic data of MADV and VEEV infections recorded since 1961 in Panama. A total of 168 human alphavirus encephalitis cases were detected in Panama during 1961‒2023. We described the clinical signs and symptoms and epidemiologic characteristics of those cases, and also explored signs and symptoms as potential predictors of encephalitic alphavirus infection compared with those of other arbovirus infections occurring in the region. Our results highlight the challenges for the clinical diagnosis of alphavirus disease in endemic regions with overlapping circulation of multiple arboviruses.