Francisella tularensis subsp. novicida isolated from a human in Arizona

<p>Abstract</p> <p>Background</p> <p><it>Francisella tularensis </it>is the etiologic agent of tularemia and is classified as a select agent by the Centers for Disease Control and Prevention. Currently four known subspecies of <it>F. tularensis </it>that differ in virulence and geographical distribution are recognized:<it>tularensis </it>(type A), <it>holarctica </it>(type B), <it>mediasiatica</it>, and <it>novicida</it>. Because of the Select Agent status and differences in virulence and geographical location, the molecular analysis of any clinical case of tularemia is of particular interest. We analyzed an unusual <it>Francisella </it>clinical isolate from a human infection in Arizona using multiple DNA-based approaches.</p> <p>Findings</p> <p>We report that the isolate is <it>F. tularensis </it>subsp. <it>novicida</it>, a subspecies that is rarely isolated.</p> <p>Conclusion</p> <p>The rarity of this <it>novicida </it>subspecies in clinical settings makes each case study important for our understanding of its role in disease and its genetic relationship with other <it>F. tularensis </it>subspecies.</p

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Executing a One Health approach during a zoonotic outbreak response

ObjectiveDemonstrate the utility of a One Health collaboration during a leptospirosis outbreak to expand outreach in human, environmental and animal health arenas.IntroductionThe One Health paradigm emphasizes cooperation and interdisciplinary collaboration to promote health and well-being among people, animals and the environment. Though the concept of One Health has been around since the 1800’s, the phrase “One Health” was more recently coined, and projects are being developed globally under its sponsorship. Maricopa County Department of Public Health (MCDPH) has been working at a local level to enhance its One Health surveillance efforts and partnerships. This One Health partnership, comprised of representatives from the Arizona Department of Agriculture (ADA), Arizona Department of Health Services (ADHS), Arizona Game and Fish Department (AzGFD), Arizona Veterinary Medicine Association (AzVMA), Centers for Disease Control &amp; Prevention (CDC), MCDPH, Midwestern University (MWU) Veterinary School, and local veterinarians, was employed during a response to the recent emergence of leptospirosis in Maricopa County, Arizona.Leptospirosis is a zoonotic bacterial disease typically prevalent in tropical regions, especially island countries or low-lying areas that flood. In the United States, CDC reports 100-200 human cases annually. Within the last five years, there have been two confirmed travel-associated human cases reported in Maricopa County. However, no locally acquired human or canine leptospirosis cases were reported.Two separate clusters of canine leptospirosis were reported in Maricopa County in 2016; the first was detected in February among canines within a household. To increase awareness in the veterinary community, the AzVMA published an article summarizing the cluster. This article might have aided in the identification of a second larger cluster in November that involved multiple veterinary and boarding facilities throughout Maricopa County. Following both clusters, capacity increased for canine and human surveillance, laboratory testing, and environmental remediation, and discussions were initiated regarding wildlife testing through the efforts of the One Health team.MethodsA coordinated review of canine medical records verified suspicion of leptospirosis within the exposed canine population. A CDC questionnaire was modified by the One Health team and facilities were visited to identify possible sources of canine infection.A Knowledge, Attitudes and Practice (KAP) survey was distributed through the AzVMA to guide veterinary education efforts. Lecture series, educational materials, and health alerts were created with input from One Health agencies for physicians, veterinarians, dog boarding facilities, and owners.CDC subject matter experts assisted in the implementation of a serosurvey of both dog owners and veterinary staff to determine if zoonotic transmission had occurred at the home, veterinary clinic or boarding facility. CDC laboratory testing provided leptospirosis speciation of canine urine specimens.ResultsMedical records were abstracted for 79 suspect leptospirosis canine cases and 48 owners were interviewed to assess their risk and exposure factors for their dogs. Prior to the visit, some facilities had already implemented self-directed infection control activities. No procedural gaps were identified at the four canine boarding facilities and veterinary clinics visited.The KAP survey was completed by 216 Arizona veterinarians and technicians. Educational outreach included three AzVMA newsletter articles distributed to approximately 1,100 registered veterinarians, one fact sheet regarding the leptospirosis vaccine, and three factsheets targeting prevention and infection control messages for boarding facilities, veterinary clinics and the home. A three-part lecture series presented jointly by ADHS, ADA, MCDPH, and MWU was attended by approximately 150 veterinarians. A health alert about the possibility of leptospirosis human cases was distributed by MCDPH to healthcare providers.Eighty-five dogs with either compatible symptoms or exposure were tested through the CDC laboratory, 68 (80%) were positive. Canine testing revealed different leptospirosis species between the two clusters, suggesting it was unlikely that they had a common source of exposure. No zoonotic transmission was identified among the 118 people tested in the serosurvey.ConclusionsPre-existing connections between public health and animal health partners helped facilitate and expand laboratory testing, diagnosis, reporting, outbreak tracking and prevention. The serosurvey provided a novel opportunity to identify cases amongst exposed people and provided insight into zoonotic transmission. Information gained from the KAP survey provided a gap analysis in veterinary services and guided education efforts. Since July 2017, no new canine cases have been reported to public health. However, further studies to identify sources of transmission in wildlife are being developed. The collaborative efforts of multiple agencies culminated in a robust outbreak response and the strengthened processes and relationships can be leveraged for future emerging diseases

Genomic Analyses of Acute Flaccid Myelitis Cases among a Cluster in Arizona Provide Further Evidence of Enterovirus D68 Role

Enteroviruses frequently result in respiratory and gastrointestinal illness; however, multiple subtypes, including poliovirus, can cause severe neurologic disease. Recent biennial increases (i.e., 2014, 2016, and 2018) in cases of non-polio acute flaccid paralysis have led to speculations that other enteroviruses, specifically enterovirus D68 (EV-D68), are emerging to fill the niche that was left from poliovirus eradication. A cluster of 11 suspect cases of pediatric acute flaccid myelitis (AFM) was identified in 2016 in Phoenix, AZ. Multiple genomic analyses identified the presence of EV-D68 in the majority of clinical AFM cases. Beyond limited detection of herpesvirus, no other likely etiologies were found in the cluster. These findings strengthen the likelihood that EV-D68 is a cause of AFM and show that the rapid molecular assays developed for this study are useful for investigations of AFM and EV-D68.Enteroviruses are a common cause of respiratory and gastrointestinal illness, and multiple subtypes, including poliovirus, can cause neurologic disease. In recent years, enterovirus D68 (EV-D68) has been associated with serious neurologic illnesses, including acute flaccid myelitis (AFM), frequently preceded by respiratory disease. A cluster of 11 suspect cases of pediatric AFM was identified in September 2016 in Phoenix, AZ. To determine if these cases were associated with EV-D68, we performed multiple genomic analyses of nasopharyngeal (NP) swabs and cerebrospinal fluid (CSF) material from the patients, including real-time PCR and amplicon sequencing targeting the EV-D68 VP1 gene and unbiased microbiome and metagenomic sequencing. Four of the 11 patients were classified as confirmed cases of AFM, and an additional case was classified as probable AFM. Real-time PCR and amplicon sequencing detected EV-D68 virus RNA in the three AFM patients from which NP swabs were collected, as well as in a fourth patient diagnosed with acute disseminated encephalomyelitis, a disease that commonly follows bacterial or viral infections, including enterovirus. No other obvious etiological causes for AFM were identified by 16S or RNA and DNA metagenomic sequencing in these cases, strengthening the likelihood that EV-D68 is an etiological factor. Herpes simplex viral DNA was detected in the CSF of the fourth case of AFM and in one additional suspect case from the cluster. Multiple genomic techniques, such as those described here, can be used to diagnose patients with suspected EV-D68 respiratory illness, to aid in AFM diagnosis, and for future EV-D68 surveillance and epidemiology