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.

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.

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.

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.

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.

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.

Contact investigation of melioidosis cases reveals regional endemicity in Puerto Rico.

BACKGROUND: Melioidosis results from infection with Burkholderia pseudomallei and is associated with case-fatality rates up to 40%. Early diagnosis and treatment with appropriate antimicrobials can improve survival rates. Fatal and nonfatal melioidosis cases were identified in Puerto Rico in 2010 and 2012, respectively, which prompted contact investigations to identify risk factors for infection and evaluate endemicity. METHODS: Questionnaires were administered and serum specimens were collected from coworkers, neighborhood contacts within 250 m of both patients' residences, and injection drug user (IDU) contacts of the 2012 patient. Serum specimens were tested for evidence of prior exposure to B. pseudomallei by indirect hemagglutination assay. Neighborhood seropositivity results guided soil sampling to isolate B. pseudomallei. RESULTS: Serum specimens were collected from contacts of the 2010 (n = 51) and 2012 (n = 60) patients, respectively. No coworkers had detectable anti-B. pseudomallei antibody, whereas seropositive results among neighborhood contacts was 5% (n = 2) for the 2010 patient and 23% (n = 12) for the 2012 patient, as well as 2 of 3 IDU contacts for the 2012 case. Factors significantly associated with seropositivity were having skin wounds, sores, or ulcers (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.2-17.8) and IDU (OR, 18.0; 95% CI, 1.6-194.0). Burkholderia pseudomallei was isolated from soil collected in the neighborhood of the 2012 patient. CONCLUSIONS: Taken together, isolation of B. pseudomallei from a soil sample and high seropositivity among patient contacts suggest at least regional endemicity of melioidosis in Puerto Rico. Increased awareness of melioidosis is needed to enable early case identification and early initiation of appropriate antimicrobial therapy.

Investigation of inhalation anthrax case, United States.

Inhalation anthrax occurred in a man who vacationed in 4 US states where anthrax is enzootic. Despite an extensive multi-agency investigation, the specific source was not detected, and no additional related human or animal cases were found. Although rare, inhalation anthrax can occur naturally in the United States.

Centers for disease control and prevention expert panel meetings on prevention and treatment of anthrax in adults.

The Centers for Disease Control and Prevention convened panels of anthrax experts to review and update guidelines for anthrax postexposure prophylaxis and treatment. The panels included civilian and military anthrax experts and clinicians with experience treating anthrax patients. Specialties represented included internal medicine, pediatrics, obstetrics, infectious disease, emergency medicine, critical care, pulmonology, hematology, and nephrology. Panelists discussed recent patients with systemic anthrax; reviews of published, unpublished, and proprietary data regarding antimicrobial drugs and anthrax antitoxins; and critical care measures of potential benefit to patients with anthrax. This article updates antimicrobial postexposure prophylaxis and antimicrobial and antitoxin treatment options and describes potentially beneficial critical care measures for persons with anthrax, including clinical procedures for infected nonpregnant adults. Changes from previous guidelines include an expanded discussion of critical care and clinical procedures and additional antimicrobial choices, including preferred antimicrobial drug treatment for possible anthrax meningitis.

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.

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.

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.

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.

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.

Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009.

These recommendations from the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations for anthrax vaccine adsorbed (AVA) (CDC. Use of anthrax vaccine in the United States: Recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2000;49:1-20; CDC. Use of anthrax vaccine in response to terrorism: supplemental recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2002;51:1024-6) and reflect the status of anthrax vaccine supplies in the United States. This statement 1) provides updated information on anthrax epidemiology; 2) summarizes the evidence regarding the effectiveness and efficacy, immunogenicity, and safety of AVA; 3) provides recommendations for pre-event and preexposure use of AVA; and 4) provides recommendations for postexposure use of AVA. In certain instances, recommendations that did not change were clarified. No new licensed anthrax vaccines are presented. Substantial changes to these recommendations include the following: 1) reducing the number of doses required to complete the pre-event and preexposure primary series from 6 doses to 5 doses, 2) recommending intramuscular rather than subcutaneous AVA administration for preexposure use, 3) recommending AVA as a component of postexposure prophylaxis in pregnant women exposed to aerosolized Bacillus anthracis spores, 4) providing guidance regarding preexposure vaccination of emergency and other responder organizations under the direction of an occupational health program, and 5) recommending 60 days of antimicrobial prophylaxis in conjunction with 3 doses of AVA for optimal protection of previously unvaccinated persons after exposure to aerosolized B. anthracis spores.

Anthrax letters in an open office environment: effects of selected CDC response guidelines on personal exposure and building contamination.

In 2001, letters filled with a powder containing anthrax (Bacillus anthracis) spores were delivered by mail to a number of governmental and media locations within the United States. In response, the U.S. Centers for Disease Control and Prevention (CDC) provided guidelines for office personnel who might encounter a letter containing suspicious powder. These guidelines were developed during the crisis and in the absence of experimental data from laboratory or field investigations. An obvious need thus exists for quantitative and scientific verification for validation of these guidelines. This study attempts to address this need, adapting earlier work that used a multiple small office test site to create a model system in an open office test site in a vacated office building in which Bacillus atrophaeus spores (as a simulant for B. anthracis spores) were released by opening a letter. Using SF(6) as a tracer gas, smoke tubes (containing stannic chloride) to visualize airflow, culturable aerosol sampling, and aerosol spectrometry we were able to characterize airflow and unmitigated spore aerosol dissemination within the office test site. Subsequently, two scripted test scenarios were used to reproduce selected portions of the existing CDC response guidelines and a modified version where the contaminated letter opener warned co-workers to evacuate then waited 5 min before doing so himself. By not leaving together with other co-workers, the risk of the letter opener cross-contaminating others was eliminated. The total potential spore aerosol exposure of the letter opener was not affected by remaining still and waiting 5 min to allow co-workers to escape first before leaving the office. Closing office doors and quickly deactivating the heating, ventilation, and air conditioning system significantly reduced spore aerosol concentrations outside the main open office in which they had been released.

Antimicrobial-resistant nocardia isolates, United States, 1995-2004.

We conducted a 10-year retrospective evaluation of the epidemiology and identification of Nocardia isolates submitted to the Centers for Disease Control and Prevention for antimicrobial susceptibility testing. The species most commonly identified were N. nova (28%), N. brasiliensis (14%), and N. farcinica (14%). Of 765 isolates submitted, 61% were resistant to sulfamethoxazole and 42% were resistant to trimethoprim-sulfamethoxazole.

Outbreak of leptospirosis among Adventure Race participants in Florida, 2005.

BACKGROUND: On 21 November 2005, a 32-year-old male resident of New York was hospitalized with suspected leptospirosis. He had participated in an endurance-length swamp race on 4-5 November 2005 outside of Tampa, Florida. METHODS: We interviewed racers to assess illness, medical care, and race activities. A suspected case was defined as fever plus > or = 2 signs or symptoms of leptospirosis occurring in a racer after 4 November 2005. Individuals with suspected cases were referred for treatment as needed and were asked to submit serum samples for microscopic agglutination testing (MAT) and for rapid testing by the dot enzyme-linked immunosorbent assay dipstick immunoglobulin M immunoassay. RESULTS: The Centers for Disease Control and Prevention and participating state health departments interviewed 192 (96%) of 200 racers from 32 states and Canada. Forty-four (23%) of 192 racers met the definition for a suspected case. The median age of the patients was 37 years (range, 19-66 years), and 128 (66.7%) were male. Fourteen (45%) of the 31 patients with suspected cases who were tested had their cases confirmed by serological testing (a single sample with MAT titer > or = 400), including the index case patient. Organisms of a potential novel serovar (species Leptospira noguchii) were isolated in culture from 1 case patient. Factors associated with increased risk of leptospirosis included swallowing river water (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.6-7.0), swallowing swamp water (OR, 2.4; 95% CI, 1.1-5.2), and being submerged in any water (OR, 2.3; 95% CI, 1.1-4.7). CONCLUSIONS: This report describes a leptospirosis outbreak that resulted in a high rate of symptomatic infection among adventure racers in Florida. The growing popularity of adventure sports may put more people at risk for leptospirosis, even in areas that have not previously been considered areas of leptospirosis endemicity.

Multigeneration cross contamination of mail with Bacillus species spores by tumbling.

In 2001, envelopes loaded with Bacillus anthracis spores were mailed to Senators Daschle and Leahy as well as to the New York Post and NBC News buildings. Additional letters may have been mailed to other news agencies because there was confirmed anthrax infection of employees at these locations. These events heightened the awareness of the lack of understanding of the mechanism(s) by which objects contaminated with a biological agent might spread disease. This understanding is crucial for the estimation of the potential for exposure to ensure the appropriate response in the event of future attacks. In this study, equipment to simulate interactions between envelopes and procedures to analyze the spread of spores from a "payload" envelope (i.e., loaded internally with a powdered spore preparation) onto neighboring envelopes were developed. Another process to determine whether an aerosol could be generated by opening contaminated envelopes was developed. Subsequent generations of contaminated envelopes originating from a single payload envelope showed a consistent two-log decrease in the number of spores transferred from one generation to the next. Opening a tertiary contaminated envelope resulted in an aerosol containing 10(3) B. anthracis spores. We developed a procedure for sampling contaminated letters by a nondestructive method aimed at providing information useful for consequence management while preserving the integrity of objects contaminated during the incident and preserving evidence for law enforcement agencies.