A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.

BACKGROUND: The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib. OBJECTIVE: To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile. DESIGN: Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579). SETTING: Sixty-seven trial sites in 8 countries. PARTICIPANTS: Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants). INTERVENTION: Baricitinib+remdesivir versus placebo+remdesivir. MEASUREMENTS: Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories. RESULTS: In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile. LIMITATION: Secondary analysis of data collected before circulation of current SARS-CoV-2 variants. CONCLUSION: The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data.

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.

Infectious Diseases Physicians: Improving and Protecting the Public's Health: Why Equitable Compensation Is Critical.

Infectious diseases (ID) physicians play a crucial role in public health in a variety of settings. Unfortunately, much of this work is undercompensated despite the proven efficacy of public health interventions such as hospital acquired infection prevention, antimicrobial stewardship, disease surveillance, and outbreak response. The lack of compensation makes it difficult to attract the best and the brightest to the field of ID, threatening the future of the ID workforce. Here, we examine compensation data for ID physicians compared to their value in population and public health settings and suggest policy recommendations to address the pay disparities that exist between cognitive and procedural specialties that prevent more medical students and residents from entering the field. All ID physicians should take an active role in promoting the value of the subspecialty to policymakers and influencers as well as trainees.

Travel-Associated Zika Virus Disease Acquired in the Americas Through February 2016: A GeoSentinel Analysis.

Background: Zika virus has spread rapidly in the Americas and has been imported into many nonendemic countries by travelers. Objective: To describe clinical manifestations and epidemiology of Zika virus disease in travelers exposed in the Americas. Design: Descriptive, using GeoSentinel records. Setting: 63 travel and tropical medicine clinics in 30 countries. Patients: Ill returned travelers with a confirmed, probable, or clinically suspected diagnosis of Zika virus disease seen between January 2013 and 29 February 2016. Measurements: Frequencies of demographic, trip, and clinical characteristics and complications. Results: Starting in May 2015, 93 cases of Zika virus disease were reported. Common symptoms included exanthema (88%), fever (76%), and arthralgia (72%). Fifty-nine percent of patients were exposed in South America; 71% were diagnosed in Europe. Case status was established most commonly by polymerase chain reaction (PCR) testing of blood and less often by PCR testing of other body fluids or serology and plaque-reduction neutralization testing. Two patients developed Guillain-Barré syndrome, and 3 of 4 pregnancies had adverse outcomes (microcephaly, major fetal neurologic abnormalities, and intrauterine fetal death). Limitation: Surveillance data collected by specialized clinics may not be representative of all ill returned travelers, and denominator data are unavailable. Conclusion: These surveillance data help characterize the clinical manifestations and adverse outcomes of Zika virus disease among travelers infected in the Americas and show a need for global standardization of diagnostic testing. The serious fetal complications observed in this study highlight the importance of travel advisories and prevention measures for pregnant women and their partners. Travelers are sentinels for global Zika virus circulation and may facilitate further transmission. Primary Funding Source: Centers for Disease Control and Prevention, International Society of Travel Medicine, and Public Health Agency of Canada.

Differential diagnosis of illness in travelers arriving from Sierra Leone, Liberia, or Guinea: a cross-sectional study from the GeoSentinel Surveillance Network.

BACKGROUND: The largest-ever outbreak of Ebola virus disease (EVD), ongoing in West Africa since late 2013, has led to export of cases to Europe and North America. Clinicians encountering ill travelers arriving from countries with widespread Ebola virus transmission must be aware of alternate diagnoses associated with fever and other nonspecific symptoms. OBJECTIVE: To define the spectrum of illness observed in persons returning from areas of West Africa where EVD transmission has been widespread. DESIGN: Descriptive, using GeoSentinel records. SETTING: 57 travel or tropical medicine clinics in 25 countries. PATIENTS: 805 ill returned travelers and new immigrants from Sierra Leone, Liberia, or Guinea seen between September 2009 and August 2014. MEASUREMENTS: Frequencies of demographic and travel-related characteristics and illnesses reported. RESULTS: The most common specific diagnosis among 770 nonimmigrant travelers was malaria (n = 310 [40.3%]), with Plasmodium falciparum or severe malaria in 267 (86%) and non-P. falciparum malaria in 43 (14%). Acute diarrhea was the second most common diagnosis among nonimmigrant travelers (n = 95 [12.3%]). Such common diagnoses as upper respiratory tract infection, urinary tract infection, and influenza-like illness occurred in only 26, 9, and 7 returning travelers, respectively. Few instances of typhoid fever (n = 8), acute HIV infection (n = 5), and dengue (n = 2) were encountered. LIMITATION: Surveillance data collected by specialist clinics may not be representative of all ill returned travelers. CONCLUSION: Although EVD may currently drive clinical evaluation of ill travelers arriving from Sierra Leone, Liberia, and Guinea, clinicians must be aware of other more common, potentially fatal diseases. Malaria remains a common diagnosis among travelers seen at GeoSentinel sites. Prompt exclusion of malaria and other life-threatening conditions is critical to limiting morbidity and mortality. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial.

BACKGROUND: Dengue virus (DENV) causes hundreds of millions of infections annually. Four dengue serotypes exist, and previous infection with one serotype increases the likelihood of severe disease with a second, heterotypic DENV infection. METHODS: In a randomized, placebo-controlled study, the safety and immunogenicity of 4 different admixtures of a live attenuated tetravalent (LATV) dengue vaccine were evaluated in 113 flavivirus-naive adults. Serum neutralizing antibody levels to all 4 dengue viruses were measured on days 0, 28, 42, and 180. RESULTS: A single dose of each LATV admixture induced a trivalent or better neutralizing antibody response in 75%-90% of vaccinees. There was no significant difference in the incidence of adverse events between vaccinees and placebo-recipients other than rash. A trivalent or better response correlated with rash and with non-black race (P < .0001). Black race was significantly associated with a reduced incidence of vaccine viremia. CONCLUSIONS: TV003 induced a trivalent or greater antibody response in 90% of flavivirus-naive vaccinees and is a promising candidate for the prevention of dengue. Race was identified as a factor influencing the infectivity of the LATV viruses, reflecting observations of the effect of race on disease severity in natural dengue infection.

Preparing the Frontlines: Delivering Special Pathogen Training to Maryland Hospital Staff.

Healthcare workers (HCWs) at community hospitals, also known as frontline hospitals (FLHs), may encounter patients with possible infectious diseases, including those caused by high-consequence pathogens such as Zaire ebolavirus. We created and piloted a 1-day, in-person, didactic and skills training program to determine the feasibility and acceptability of implementing an educational program to enhance the knowledge and skills needed to respond when a patient with a potential high-consequence pathogen presents to an FLH. The Maryland Department of Health queried all 104 state FLHs to identify their interest in participating in the pilot training program. HCWs from 12 (75%) of the 16 interested FLHs participated in the program before it was interrupted by the COVID-19 pandemic. In addition to pathogen-specific training based on the Identify, Isolate, and Inform framework, we provided skills training in the proper use of personal protective equipment, spill cleanup, and removal of an incapacitated HCW from an isolation area. We conducted a paired pretraining and posttraining knowledge assessment and measured a significant learning gain among 135 participants (2-tailed t test, P<.05). Over 95% of the participants reported that the training was relevant to their daily work and the clinical simulations and reference material were useful and appropriate for their learning level. Findings from this pilot program demonstrated the feasibility and acceptability of a 1-day combined didactic and skills training program focused on high-consequence pathogens. We plan to reengage the original FLHs and add regional FLHs in an updated training effort based on our findings.

Baricitinib Treatment of Coronavirus Disease 2019 Is Associated With a Reduction in Secondary Infections.

We performed a secondary analysis of the National Institutes of Health-sponsored Adaptive COVID-19 Treatment Trial (ACTT-2) randomized controlled trial and found that baricitinib was associated with a 50% reduction in secondary infections after controlling for baseline and postrandomization patient characteristics. This finding provides a novel mechanism of benefit for baricitinib and supports the safety profile of this immunomodulator for the treatment of coronavirus disease 2019.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Global TravEpiNet: a national consortium of clinics providing care to international travelers--analysis of demographic characteristics, travel destinations, and pretravel healthcare of high-risk US international travelers, 2009-2011.

BACKGROUND: International travel poses a risk of destination-specific illness and may contribute to the global spread of infectious diseases. Despite this, little is known about the health characteristics and pretravel healthcare of US international travelers, particularly those at higher risk of travel-associated illness. METHODS: We formed a national consortium (Global TravEpiNet) of 18 US clinics registered to administer yellow fever vaccination. We collected data regarding demographic and health characteristics, destinations, purpose of travel, and pretravel healthcare from 13235 international travelers who sought pretravel consultation at these sites from January 2009 through January 2011. RESULTS: The destinations and itineraries of Global TravEpiNet travelers differed from those of the overall population of US international travelers. The majority of Global TravEpiNet travelers were visiting low- or lower-middle-income countries, and Africa was the most frequently visited region. Seventy-five percent of travelers were visiting malaria-endemic countries, and 38% were visiting countries endemic for yellow fever. Fifty-nine percent of travelers reported ≥1 medical condition. Atovaquone/proguanil was the most commonly prescribed antimalarial drug, and most travelers received an antibiotic for self-treatment of travelers' diarrhea. Hepatitis A and typhoid were the most frequently administered vaccines. CONCLUSIONS: Data from Global TravEpiNet provide insight into the characteristics and pretravel healthcare of US international travelers who are at increased risk of travel-associated illness due to itinerary, purpose of travel, or existing medical conditions. Improved understanding of this epidemiologically significant population may help target risk-reduction strategies and interventions to limit the spread of infections related to global travel.

The Use of Temperature and Pressure Data Loggers to Validate the Steam Sterilization of Category A Clinical Waste.

Introduction: Over the past decade, there have been outbreaks associated with high consequence infectious diseases such as Ebola virus disease, Lassa fever, and Monkeypox. The proper handling of clinical waste from patients infected with such pathogens is critical to ensure healthcare personnel and community safety. Methods: Mock clinical waste bags were created to simulate four distinct waste streams: personal protective equipment (PPE), dry linens, wet linens, and solidified liquids. Pressure and temperature data loggers were buried in the middle of simulated waste loads to record time at a sterilization temperature of 132°C (270°F) to reduce sterilization time. We also validated super rapid biological indicators (BIs) by embedding standard BIs (48 h), rapid BIs (3 h), and super rapid BIs (24 min) within each load. Cycles were validated over a 2-day period, using a total of 36 simulated waste bags (6 bags each for PPE, dry linen, and wet linen, and 18 bags for solidified liquids). Results: All waste bags achieved the target sterilization temperature, all BIs passed and cycle times were substantially decreased. For PPE waste processing, an estimated 15 h was saved for a 24-h period. Discussion: Default factory settings are inadequate to disinfect Category A clinical waste. Reliance on autoclave temperature readings may overestimate time at goal sterilization temperature for actual waste loads. Conclusions: The data provided by within bag data loggers and BIs allow for the optimization of autoclave parameters to increase throughput and enhance staff safety.

The role of dedicated biocontainment patient care units in preparing for COVID-19 and other infectious disease outbreaks.

In response to the Ebola outbreak of 2014-2016, the US Office of the Assistant Secretary for Preparedness and Response (ASPR) established 10 regional treatment centers, called biocontainment units (BCUs), to prepare and provide care for patients infected with high-consequence pathogens. Many of these BCUs were among the first units to activate for coronavirus disease 2019 (COVID-19) patient care. The activities of the Johns Hopkins BCU helped prepare the Johns Hopkins Health System for COVID-19 in the 3 domains of containment care: (1) preparedness planning, education and training, (2) patient care and unit operations, and (3) research and innovation. Here, we describe the role of the JH BCU in the Hopkins COVID-19 response to illustrate the value of BCUs in the current pandemic and their potential role in preparing healthcare facilities and health systems for future infectious disease threats.

The Risk of Not Being Ready: A Novel Approach to Managing Constant Readiness of a High-Level Isolation Unit During Times of Inactivity.

The biocontainment unit at Johns Hopkins Hospital is a specially designed, inactive high-level isolation unit designated to care for patients infected with high-consequence pathogens. The unit team designed a facility-specific readiness scale and checklist that focus on infrastructure, consumable supplies, and staffing to assess activation readiness of the biocontainment unit. Over a period of 50 days and 14 days, these tools were used as part of a routine risk assessment to first identify barriers and then tier the impact of these barriers into activation categories of "Ready," "Ready with Considerations," and "Not Ready." The assessment identified the greatest risks to activation readiness were staffing and waste management capabilities. Assessing threats to activation readiness and the risk of not being ready should be a priority for maintaining facility, regional, and national capacity to safely isolate and care for patients infected with high-consequence pathogens while maintaining healthcare worker safety.

Zika among international travellers presenting to GeoSentinel sites, 2012-2019: implications for clinical practice.

INTRODUCTION: International travellers contribute to the rapid spread of Zika virus (ZIKV) and its sentinel identification globally. We describe ZIKV infections among international travellers seen at GeoSentinel sites with a focus on ZIKV acquired in the Americas and the Caribbean, describe countries of exposure and traveller characteristics, and assess ZIKV diagnostic testing by site. METHODS: Records with an international travel-related diagnosis of confirmed or probable ZIKV from January 2012 through December 2019 reported to GeoSentinel with a recorded illness onset date were included to show reported cases over time. Records from March 2016 through December 2019 with an exposure region of the Americas or the Caribbean were included in the descriptive analysis. A survey was conducted to assess the availability, accessibility and utilization of ZIKV diagnostic tests at GeoSentinel sites. RESULTS: GeoSentinel sites reported 525 ZIKV cases from 2012 through 2019. Between 2012 and 2014, eight cases were reported, and all were acquired in Asia or Oceania. After 2014, most cases were acquired in the Americas or the Caribbean, a large decline in ZIKV cases occurred in 2018-19.Between March 2016 and December 2019, 423 patients acquired ZIKV in the Americas or the Caribbean, peak reporting to these regions occurred in 2016 [330 cases (78%)]. The median age was 36 years (range: 3-92); 63% were female. The most frequent region of exposure was the Caribbean (60%). Thirteen travellers were pregnant during or after travel; one had a sexually acquired ZIKV infection. There was one case of fetal anomaly and two travellers with Guillain-Barré syndrome. GeoSentinel sites reported various challenges to diagnose ZIKV effectively. CONCLUSION: ZIKV should remain a consideration for travellers returning from areas with risk of ZIKV transmission. Travellers should discuss their travel plans with their healthcare providers to ensure ZIKV prevention measures are taken.

Cutaneous and mucocutaneous leishmaniasis in travellers and migrants: a 20-year GeoSentinel Surveillance Network analysis.

BACKGROUND: Cutaneous leishmaniasis (CL) may be emerging among international travellers and migrants. Limited data exist on mucocutaneous leishmaniasis (MCL) in travellers. We describe the epidemiology of travel-associated CL and MCL among international travellers and immigrants over a 20-year period through descriptive analysis of GeoSentinel data. METHODS: Demographic and travel-related data on returned international travellers diagnosed with CL or MCL at a GeoSentinel Surveillance Network site between 1 September 1997 and 31 August 2017 were analysed. RESULTS: A total of 955 returned travellers or migrants were diagnosed with travel-acquired CL (n = 916) or MCL during the study period, of whom 10% (n = 97) were migrants. For the 858 non-migrant travellers, common source countries were Bolivia (n = 156, 18.2%) and Costa Rica (n = 97, 11.3%), while for migrants, they were Syria (n = 34, 35%) and Afghanistan (n = 22, 22.7%). A total of 99 travellers (10%) acquired their disease on trips of ≤ 2 weeks. Of 274 cases for which species identification was available, Leishmania Viannia braziliensis was the most well-represented strain (n = 117, 42.7%), followed by L. major (n = 40, 14.6%) and L. V. panamensis (n = 38, 13.9%). Forty cases of MCL occurred, most commonly in tourists (n = 29, 72.5%) and from Bolivia (n = 18, 45%). A total of 10% of MCL cases were acquired in the Old World. CONCLUSIONS: Among GeoSentinel reporting sites, CL is predominantly a disease of tourists travelling mostly to countries in Central and South America such as Bolivia where risk of acquiring L. V. braziliensis and subsequent MCL is high. The finding that some travellers acquired leishmaniasis on trips of short duration challenges the common notion that CL is a disease of prolonged travel. Migrants from areas of conflict and political instability, such as Afghanistan and Syria, were well represented, suggesting that as mass migration of refugees continues, CL will be increasingly encountered in intake countries.

Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis-1997-2016.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.