Investigating the etiology of acute febrile illness: a prospective clinic-based study in Uganda.

BACKGROUND: Historically, malaria has been the predominant cause of acute febrile illness (AFI) in sub-Saharan Africa. However, during the last two decades, malaria incidence has declined due to concerted public health control efforts, including the widespread use of rapid diagnostic tests leading to increased recognition of non-malarial AFI etiologies. Our understanding of non-malarial AFI is limited due to lack of laboratory diagnostic capacity. We aimed to determine the etiology of AFI in three distinct regions of Uganda. METHODS: A prospective clinic-based study that enrolled participants from April 2011 to January 2013 using standard diagnostic tests. Participant recruitment was from St. Paul's Health Centre (HC) IV, Ndejje HC IV, and Adumi HC IV in the western, central and northern regions, which differ by climate, environment, and population density. A Pearson's chi-square test was used to evaluate categorical variables, while a two-sample t-test and Krukalis-Wallis test were used for continuous variables. RESULTS: Of the 1281 participants, 450 (35.1%), 382 (29.8%), and 449 (35.1%) were recruited from the western, central, and northern regions, respectively. The median age (range) was 18 (2-93) years; 717 (56%) of the participants were female. At least one AFI pathogen was identified in 1054 (82.3%) participants; one or more non-malarial AFI pathogens were identified in 894 (69.8%) participants. The non-malarial AFI pathogens identified were chikungunya virus, 716 (55.9%); Spotted Fever Group rickettsia (SFGR), 336 (26.2%) and Typhus Group rickettsia (TGR), 97 (7.6%); typhoid fever (TF), 74 (5.8%); West Nile virus, 7 (0.5%); dengue virus, 10 (0.8%) and leptospirosis, 2 (0.2%) cases. No cases of brucellosis were identified. Malaria was diagnosed either concurrently or alone in 404 (31.5%) and 160 (12.5%) participants, respectively. In 227 (17.7%) participants, no cause of infection was identified. There were statistically significant differences in the occurrence and distribution of TF, TGR and SFGR, with TF and TGR observed more frequently in the western region (p = 0.001; p < 0.001) while SFGR in the northern region (p < 0.001). CONCLUSION: Malaria, arboviral infections, and rickettsioses are major causes of AFI in Uganda. Development of a Multiplexed Point-of-Care test would help identify the etiology of non-malarial AFI in regions with high AFI rates.

Development of core competencies for field veterinary epidemiology training programs.

A workforce with the adequate field epidemiology knowledge, skills and abilities is the foundation of a strong and effective animal health system. Field epidemiology training is conducted in several countries to meet the increased global demand for such a workforce. However, core competencies for field veterinary epidemiology have not been identified and agreed upon globally, leading to the development of different training curricula. Having a set of agreed core competencies can harmonize field veterinary epidemiology training. The Food and Agriculture Organization of the United Nations (FAO) initiated a collective, iterative, and participative process to achieve this and organized two expert consultative workshops in 2018 to develop core competencies for field veterinary epidemiology at the frontline and intermediate levels. Based on these expert discussions, 13 competencies were identified for the frontline and intermediate levels. These competencies were organized into three domains: epidemiological surveillance and studies; field investigation, preparedness and response; and One Health, communication, ethics and professionalism. These competencies can be used to facilitate the development of field epidemiology training curricula for veterinarians, adapted to country training needs, or customized for training other close disciplines. The competencies can also be useful for mentors and employers to monitor and evaluate the progress of their mentees, or to guide the selection process during the recruitment of new staff.

One health systems strengthening in countries: Tripartite tools and approaches at the human-animal-environment interface.

Unexpected pathogen transmission between animals, humans and their shared environments can impact all aspects of society. The Tripartite organisations-the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH)-have been collaborating for over two decades. The inclusion of the United Nations Environment Program (UNEP) with the Tripartite, forming the 'Quadripartite' in 2021, creates a new and important avenue to engage environment sectors in the development of additional tools and resources for One Health coordination and improved health security globally. Beginning formally in 2010, the Tripartite set out strategic directions for the coordination of global activities to address health risks at the human-animal-environment interface. This paper highlights the historical background of this collaboration in the specific area of health security, using country examples to demonstrate lessons learnt and the evolution and pairing of Tripartite programmes and processes to jointly develop and deliver capacity strengthening tools to countries and strengthen performance for iterative evaluations. Evaluation frameworks, such as the International Health Regulations (IHR) Monitoring and Evaluation Framework, the WOAH Performance of Veterinary Services (PVS) Pathway and the FAO multisectoral evaluation tools for epidemiology and surveillance, support a shared global vision for health security, ultimately serving to inform decision making and provide a systematic approach for improved One Health capacity strengthening in countries. Supported by the IHR-PVS National Bridging Workshops and the development of the Tripartite Zoonoses Guide and related operational tools, the Tripartite and now Quadripartite, are working alongside countries to address critical gaps at the human-animal-environment interface.

Strengthening the global one health workforce: Veterinarians in CDC-supported field epidemiology training programs.

Background: Effective prevention, detection, and response to disease threats at the human-animal-environment interface rely on a multisectoral, One Health workforce. Since 2009, the U.S. Centers for Disease Control and Prevention (CDC) has supported Field Epidemiology Training Programs (FETPs) to train veterinarians and veterinary paraprofessionals (VPPs) alongside their human health counterparts in the principles of epidemiology, disease surveillance, and outbreak investigations. We aim to describe and evaluate characteristics of CDC-supported FETPs enrolling veterinarians/VPPs to understand these programs contribution to the strengthening of the global One Health workforce. Methods: We surveyed staff from CDC-supported FETPs that enroll veterinarians and VPPs regarding cohort demographics, graduate retention, and veterinary and One Health relevant curriculum inclusion. Descriptive data was analyzed using R Version 3.5.1. Results: Forty-seven FETPs reported veterinarian/VPP trainees, 68% responded to our questionnaire, and 64% reported veterinary/VPP graduates in 2017. The veterinary/VPP graduates in 2017 made up 12% of cohorts. Programs reported 74% of graduated veterinarians/VPPs retained employment within national ministries of agriculture. Common veterinary and One Health curriculum topics were specimen collection and submission (93%), zoonotic disease (90%) and biosafety practices (83%); least covered included animal/livestock production and health promotion (23%) and transboundary animal diseases (27%). Less than half (41%) of programs reported the curriculum being sufficient for veterinarians/VPPs to perform animal health specific job functions, despite most programs being linked to the ministry of agriculture (75%) and providing veterinary-specific mentorship (63%). Conclusions: Our results indicate that FETPs provide valuable training opportunities for animal health sector professionals, strengthening the epidemiology capacity within the ministries retaining them. While veterinary/VPP trainees could benefit from the inclusion of animal-specific curricula needed to fulfill their job functions, at present, FETPs continue to serve as multisectoral, competency-based, in-service training important in strengthening the global One Health workforce by jointly training the animal and human health sectors.

Seasonality and Ecological Suitability Modelling for Anthrax (Bacillus anthracis) in Western Africa.

Anthrax is hyper-endemic in West Africa affecting wildlife, livestock and humans. Prediction is difficult due to the lack of accurate outbreak data. However, predicting the risk of infection is important for public health, wildlife conservation and livestock economies. In this study, the seasonality of anthrax outbreaks in West Africa was investigated using climate time series and ecological niche modeling to identify environmental factors related to anthrax occurrence, develop geospatial risk maps and identify seasonal patterns. Outbreak data in livestock, wildlife and humans between 2010 and 2018 were compiled from different sources and analyzed against monthly rates of change in precipitation, normalized difference vegetation index (NDVI) and land surface temperature. Maximum Entropy was used to predict and map the environmental suitability of anthrax occurrence. The findings showed that: (i) Anthrax outbreaks significantly (99%) increased with incremental changes in monthly precipitation and vegetation growth and decremental changes in monthly temperature during January-June. This explains the occurrence of the anthrax peak during the early wet season in West Africa. (ii) Livestock density, precipitation seasonality, NDVI and alkaline soils were the main predictors of anthrax suitability. (iii) Our approach optimized the use of limited and heterogeneous datasets and ecological niche modeling, demonstrating the value of integrated disease notification data and outbreak reports to generate risk maps. Our findings can inform public, animal and environmental health and enhance national and regional One Health disease control strategies.

A generalizable one health framework for the control of zoonotic diseases.

Effectively preventing and controlling zoonotic diseases requires a One Health approach that involves collaboration across sectors responsible for human health, animal health (both domestic and wildlife), and the environment, as well as other partners. Here we describe the Generalizable One Health Framework (GOHF), a five-step framework that provides structure for using a One Health approach in zoonotic disease programs being implemented at the local, sub-national, national, regional, or international level. Part of the framework is a toolkit that compiles existing resources and presents them following a stepwise schematic, allowing users to identify relevant resources as they are required. Coupled with recommendations for implementing a One Health approach for zoonotic disease prevention and control in technical domains including laboratory, surveillance, preparedness and response, this framework can mobilize One Health and thereby enhance and guide capacity building to combat zoonotic disease threats at the human-animal-environment interface.

United Against Rabies Forum: The One Health Concept at Work.

Human deaths from rabies are preventable and can be eliminated by applying a systematic One Health approach. However, this ancient disease still threatens the lives of millions of people in up to 150 countries and kills an estimated 59, 000 people every year. Rabies today is largely a disease of poverty, almost always linked to dog bites, with most deaths occurring in neglected communities in Africa and Asia. The disease places an immense economic burden on its victims, a cost that far outweighs the investment needed to control it. A global framework for rabies elimination in humans is set out in Zero by 30: The Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. Despite the existence of proven control strategies and agreement on the path to eliminating human rabies deaths, mortality numbers from rabies remain high, and COVID-19 has set back efforts even further. But COVID-19 has also highlighted the value of a One Health approach to zoonotic disease and pandemic prevention. Rabies control programs offer a practical route to building One Health capacities that can also address other zoonotic threats, including those with pandemic potential. The United Against Rabies Forum aims to accelerate progress on rabies elimination while applying a One Health approach. The Forum promotes cross-sector collaboration among stakeholders and supports countries in their rabies elimination efforts. Increased political engagement and resource mobilization, both internationally and nationally, will be needed to achieve global rabies goals and can also make One Health implementation a reality.

Role of Oral Rabies Vaccines in the Elimination of Dog-Mediated Human Rabies Deaths.

Domestic dogs are responsible for nearly all the ¼59,000 global human rabies deaths that occur annually. Numerous control measures have been successful at eliminating dog-mediated human rabies deaths in upper-income countries, including dog population management, parenteral dog vaccination programs, access to human rabies vaccines, and education programs for bite prevention and wound treatment. Implementing these techniques in resource-poor settings can be challenging; perhaps the greatest challenge is maintaining adequate herd immunity in free-roaming dog populations. Oral rabies vaccines have been a cornerstone in rabies virus elimination from wildlife populations; however, oral vaccines have never been effectively used to control dog-mediated rabies. Here, we convey the perspectives of the World Organisation for Animal Health Rabies Reference Laboratory Directors, the World Organisation for Animal Health expert committee on dog rabies control, and World Health Organization regarding the role of oral vaccines for dogs. We also issue recommendations for overcoming hesitations to expedited field use of appropriate oral vaccines.

Potential distributions of Bacillus anthracis and Bacillus cereus biovar anthracis causing anthrax in Africa.

BACKGROUND: Bacillus cereus biovar anthracis (Bcbva) is an emergent bacterium closely related to Bacillus anthracis, the etiological agent of anthrax. The latter has a worldwide distribution and usually causes infectious disease in mammals associated with savanna ecosystems. Bcbva was identified in humid tropical forests of Côte d'Ivoire in 2001. Here, we characterize the potential geographic distributions of Bcbva in West Africa and B. anthracis in sub-Saharan Africa using an ecological niche modeling approach. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced occurrence data for B. anthracis and Bcbva were obtained from public data repositories and the scientific literature. Combinations of temperature, humidity, vegetation greenness, and soils values served as environmental variables in model calibrations. To predict the potential distribution of suitable environments for each pathogen across the study region, parameter values derived from the median of 10 replicates of the best-performing model for each pathogen were used. We found suitable environments predicted for B. anthracis across areas of confirmed and suspected anthrax activity in sub-Saharan Africa, including an east-west corridor from Ethiopia to Sierra Leone in the Sahel region and multiple areas in eastern, central, and southern Africa. The study area for Bcbva was restricted to West and Central Africa to reflect areas that have likely been accessible to Bcbva by dispersal. Model predicted values indicated potential suitable environments within humid forested environments. Background similarity tests in geographic space indicated statistical support to reject the null hypothesis of similarity when comparing environments associated with B. anthracis to those of Bcbva and when comparing humidity values and soils values individually. We failed to reject the null hypothesis of similarity when comparing environments associated with Bcbva to those of B. anthracis, suggesting that additional investigation is needed to provide a more robust characterization of the Bcbva niche. CONCLUSIONS/SIGNIFICANCE: This study represents the first time that the environmental and geographic distribution of Bcbva has been mapped. We document likely differences in ecological niche-and consequently in geographic distribution-between Bcbva and typical B. anthracis, and areas of possible co-occurrence between the two. We provide information crucial to guiding and improving monitoring efforts focused on these pathogens.

Knowledge, attitudes, and practices related to anthrax and animal care: A case-control study in Georgia.

INTRODUCTION: Anthrax is endemic in Georgia and recent outbreaks prompted a livestock-handler case-control study with a component to evaluate anthrax knowledge, attitudes, and practices (KAP) among livestock handlers or owners. METHODS: Cases were handlers of livestock with confirmed animal anthrax from June 2013-May 2015. Handlers of four matched unaffected animals were selected as controls, two from the same village as the case animal ("village control") and two from 3-10 km away ("area control"). Descriptive statistics were reported and conditional logistic regression was performed to estimate the magnitude of the association of cases with specific study KAP factors. RESULTS: Cases were more likely male, had lower level college education, less animal care experience, and provided more animal care to their cattle. Cases had lower odds of burying a suddenly dead animal compared to all controls (Odds Ratio [OR]: 0.32, 95% Confidence interval [CI]:0.12, 0.88) and area controls (OR: 0.32, 95% CI: 0.11, 0.91). On an 8-point knowledge scale, cases having an animal with anthrax had a 1.31 times greater knowledge score compared to all controls (95% CI: 1.03, 1.67). Cases had higher odds of ever having human anthrax or knowing another person who had anthrax compared to all controls (OR: 4.56, 95% CI: 1.45, 14.30) and area controls (OR: 7.16, 95% CI: 1.52, 33.80). DISCUSSION: Cases were more knowledgeable of anthrax and had better anthrax prevention practices, but these are likely a result of the case investigation and ring vaccination following the death of their animal. CONCLUSIONS: The findings reveal a low level of knowledge and practices related to anthrax control and prevention, and will guide educational material development to fill these gaps.

Risk factors associated with the occurrence of anthrax outbreaks in livestock in the country of Georgia: A case-control investigation 2013-2015.

INTRODUCTION: Anthrax is considered endemic in livestock in Georgia. In 2007, the annual vaccination became the responsibility of livestock owners, while contracting of private veterinarians was not officially required. Six years later, due to increase in human outbreaks associated with livestock handling, there is a need to find out the risk factors of livestock anthrax in Georgia. OBJECTIVE: To identify exposures and risk factors associated with livestock anthrax. METHODS: A matched case-control study design was used to recruit the owners of individual livestock anthrax cases that occurred between June 2013 and May 2015, and owners of unaffected livestock from within ("village control") and outside the village ("area control"). We collected data about the case and control livestock animals' exposure and risk factors within the one-month prior to the disease onset of the case livestock (or matched case for the controls). We used logistic regression analysis (univariate and multivariable) to calculate the odds ratios of exposures and risk factors. RESULTS: During the study period, 36 anthrax cases met the case definition and were enrolled in the study; 67 matched village control livestock and 71 matched area control livestock were also enrolled. The findings from multivariable logistic regression analysis demonstrate that vaccination within the last two years significantly reduced the odds of anthrax in cattle (OR = 0.014; 95% Confidence interval = <0.001, 0.99). The other factors that were significantly protective against anthrax were 'animals being in covered fence area/barn' (OR = 0.065; p-value = 0.036), and 'female animal being pregnant or milking compared to heifer' (OR = 0.006; p-value = 0.037). CONCLUSIONS: The information obtained from this study has involved and been presented to decision makers, used to build technical capacity of veterinary staff, and to foster a One Health approach to the control of zoonotic diseases which will optimize prevention and control strategies. Georgia has embedded the knowledge and specific evidence that vaccination is a highly protective measure to prevent anthrax deaths among livestock, to which primary emphasis of the anthrax control program will be given. Education of livestock keepers in Georgia is an overriding priority.

Bacillus anthracis gamma phage lysis among soil bacteria: an update on test specificity.

BACKGROUND: Bacillus anthracis, which causes anthrax in humans and animals, is enzootic in parts of the U.S. state of Texas where cases are typically reported in animals annually. The gamma phage lysis assay is a common diagnostic method for identification of B. anthracis and is based on the bacterium's susceptibility to lysis. This test has been shown to be 97% specific for B. anthracis, as a small number of strains of other Bacillus spp. are known to be susceptible. In this study, we evaluated the performance of a combination of B. anthracis diagnostic assays on 700 aerobic, spore-forming isolates recovered from soil collected in Texas. These assays include phenotypic descriptions, gamma phage susceptibility, and real-time polymerase chain reaction specific for B. anthracis. Gamma phage-susceptible isolates were also tested using cell wall and capsule direct fluorescent-antibody assays specific for B. anthracis. Gamma phage-susceptible isolates that were ruled out as B. anthracis were identified by 16S rRNA gene sequencing. FINDINGS: We identified 29 gamma phage-susceptible isolates. One was confirmed as B. anthracis, while the other 28 isolates were ruled out for B. anthracis by the other diagnostic tests. Using 16S rRNA gene sequencing results, we identified these isolates as members of the B. cereus group, Bacillus sp. (not within B. cereus group), Lysinibacillus spp., and Solibacillus silvestris. Based on these results, we report a specificity of 96% for gamma phage lysis as a diagnostic test for B. anthracis, and identified susceptible isolates outside the Bacillus genus. CONCLUSIONS: In this study we found gamma phage susceptibility to be consistent with previously reported results. However, we identified non-B. anthracis environmental isolates (including isolates from genera other than Bacillus) that are susceptible to gamma phage lysis. To date, susceptibility to gamma phage lysis has not been reported in genera other than Bacillus. Though these isolates are not of clinical origin, description of unexpected positives is important, especially as new diagnostic assays for B. anthracis are being developed based on gamma phage lysis or gamma phage proteins.

Role of Food Insecurity in Outbreak of Anthrax Infections among Humans and Hippopotamuses Living in a Game Reserve Area, Rural Zambia.

In September 2011, a total of 511 human cases of anthrax (Bacillus anthracis) infection and 5 deaths were reported in a game management area in the district of Chama, Zambia, near where 85 hippopotamuses (Hippopotamus amphibious) had recently died of suspected anthrax. The human infections generally responded to antibiotics. To clarify transmission, we conducted a cross-sectional, interviewer-administered household survey in villages where human anthrax cases and hippopotamuses deaths were reported. Among 284 respondents, 84% ate hippopotamus meat before the outbreak. Eating, carrying, and preparing meat were associated with anthrax infection. Despite the risk, 23% of respondents reported they would eat meat from hippopotamuses found dead again because of food shortage (73%), lack of meat (12%), hunger (7%), and protein shortage (5%). Chronic food insecurity can lead to consumption of unsafe foods, leaving communities susceptible to zoonotic infection. Interagency cooperation is necessary to prevent outbreaks by addressing the root cause of exposure, such as food insecurity.

Anthrax Cases Associated with Animal-Hair Shaving Brushes.

During the First World War, anthrax cases in the United States and England increased greatly and seemed to be associated with use of new shaving brushes. Further investigation revealed that the source material and origin of shaving brushes had changed during the war. Cheap brushes of imported horsehair were being made to look like the preferred badger-hair brushes. Unfortunately, some of these brushes were not effectively disinfected and brought with them a nasty stowaway: Bacillus anthracis. A review of outbreak summaries, surveillance data, and case reports indicated that these cases originated from the use of ineffectively disinfected animal-hair shaving brushes. This historical information is relevant to current public health practice because renewed interest in vintage and animal-hair shaving brushes has been seen in popular culture. This information should help healthcare providers and public health officials answer questions on this topic.

Leptospira seropositivity as a risk factor for Mesoamerican Nephropathy.

BACKGROUND: Leptospirosis is postulated as a possible cause of Mesoamerican Nephropathy (MeN) in Central American workers. OBJECTIVES: Investigate job-specific Leptospira seroprevalence and its association with kidney disease biomarkers. METHODS: In 282 sugarcane workers, 47 sugarcane applicants and 160 workers in other industries, we measured anti-leptospiral antibodies, serum creatinine, and urinary injury biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and N-acetyl-D-glucosaminidase (NAG). RESULTS: Leptospira seroprevalence differed among job categories and was highest among sugarcane cutters (59%). Seropositive sugarcane workers had higher NGAL concentrations (relative mean: 1.28; 95% CI: 0.94-1.75) compared to those who were seronegative, with similar findings among field and non-field workers. CONCLUSIONS: Leptospira seroprevalence varied by job category. There was some indication that seropositivity was associated with elevated biomarker levels, but results were inconsistent. Additional studies may help establish whether Leptospira infection plays any role in MeN among Central American workers.

Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009-2010.

We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009-2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0-5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6-11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak.

Modeling Tool for Decision Support during Early Days of an Anthrax Event.

Health officials lack field-implementable tools for forecasting the effects that a large-scale release of Bacillus anthracis spores would have on public health and hospitals. We created a modeling tool (combining inhalational anthrax caseload projections based on initial case reports, effects of variable postexposure prophylaxis campaigns, and healthcare facility surge capacity requirements) to project hospitalizations and casualties from a newly detected inhalation anthrax event, and we examined the consequences of intervention choices. With only 3 days of case counts, the model can predict final attack sizes for simulated Sverdlovsk-like events (1979 USSR) with sufficient accuracy for decision making and confirms the value of early postexposure prophylaxis initiation. According to a baseline scenario, hospital treatment volume peaks 15 days after exposure, deaths peak earlier (day 5), and recovery peaks later (day 23). This tool gives public health, hospital, and emergency planners scenario-specific information for developing quantitative response plans for this threat.

Postexposure Prophylaxis After Possible Anthrax Exposure: Adherence and Adverse Events.

Anthrax postexposure prophylaxis (PEP) was recommended to 42 people after a laboratory incident that involved potential aerosolization of Bacillus anthracis spores in 2 laboratories at the Centers for Disease Control and Prevention in 2014. At least 31 (74%) individuals who initiated PEP did not complete either the recommended 60 days of antimicrobial therapy or the 3-dose vaccine regimen. Among the 29 that discontinued the antimicrobial component of PEP, most (38%) individuals discontinued PEP because of their low perceived risk of infection; 9 (31%) individuals discontinued prophylaxis due to PEP-related minor adverse events, and 10% cited both low risk and adverse events as their reason for discontinuation. Most minor adverse events reported were gastrointestinal complaints, and none required medical attention. Individuals taking ciprofloxacin were twice as likely (RR = 2.02, 95% CI = 1.1-3.6) to discontinue antimicrobial prophylaxis when compared to those taking doxycycline. In the event anthrax PEP is recommended, public health messages and patient education materials will need to address potential misconceptions regarding exposure risk and provide information about possible adverse events in order to promote PEP adherence.

Multigeneration Cross-Contamination of Mail with Bacillus anthracis Spores.

The release of biological agents, including those which could be used in biowarfare or bioterrorism in large urban areas, has been a concern for governments for nearly three decades. Previous incidents from Sverdlosk and the postal anthrax attack of 2001 have raised questions on the mechanism of spread of Bacillus anthracis spores as an aerosol or contaminant. Prior studies have demonstrated that Bacillus atrophaeus is easily transferred through simulated mail handing, but no reports have demonstrated this ability with Bacillus anthracis spores, which have morphological differences that may affect adhesion properties between spore and formite. In this study, equipment developed to simulate interactions across three generations of envelopes subjected to tumbling and mixing was used to evaluate the potential for cross-contamination of B. anthracis spores in simulated mail handling. In these experiments, we found that the potential for cross-contamination through letter tumbling from one generation to the next varied between generations while the presence of a fluidizer had no statistical impact on the transfer of material. Likewise, the presence or absence of a fluidizer had no statistically significant impact on cross-contamination levels or reaerosolization from letter opening.

Early Indicators of Fatal Leptospirosis during the 2010 Epidemic in Puerto Rico.

BACKGROUND: Leptospirosis is a potentially fatal bacterial zoonosis that is endemic throughout the tropics and may be misdiagnosed as dengue. Delayed hospital admission of leptospirosis patients is associated with increased mortality. METHODOLOGY/PRINCIPAL FINDINGS: During a concurrent dengue/leptospirosis epidemic in Puerto Rico in 2010, suspected dengue patients that tested dengue-negative were tested for leptospirosis. Fatal and non-fatal hospitalized leptospirosis patients were matched 1:1-3 by age. Records from all medical visits were evaluated for factors associated with fatal outcome. Among 175 leptospirosis patients identified (4.7 per 100,000 residents), 26 (15%) were fatal. Most patients were older males and had illness onset during the rainy season. Fatal case patients first sought medical care earlier than non-fatal control patients (2.5 vs. 5 days post-illness onset [DPO], p < 0.01), but less frequently first sought care at a hospital (52.4% vs. 92.2%, p < 0.01). Although fatal cases were more often diagnosed with leptospirosis at first medical visit (43.9% vs. 9.6%, p = 0.01), they were admitted to the hospital no earlier than non-fatal controls (4.5 vs. 6 DPO, p = 0.31). Cases less often developed fever (p = 0.03), but more often developed jaundice, edema, leg pain, hemoptysis, and had a seizure (p ≤ 0.03). Multivariable analysis of laboratory values from first medical visit associated with fatal outcome included increased white blood cell (WBC) count with increased creatinine (p = 0.001), and decreased bicarbonate with either increased WBC count, increased creatinine, or decreased platelet count (p < 0.001). CONCLUSIONS/SIGNIFICANCE: Patients with fatal leptospirosis sought care earlier, but were not admitted for care any earlier than non-fatal patients. Combinations of routine laboratory values predictive of fatal outcome should be considered in admission decision-making for patients with suspected leptospirosis.