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Abstract 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

ABSTRACT: Objectives: To describe the characteristics of nosocomial cases of Ebola virus disease (EVD) in the Democratic Republic of the Congo between July 2018 and May 2020 in order to inform future interventions. Methods: Nosocomial cases of EVD were identified during outbreak response surveillance, and a retrospective analysis of cases was conducted according to demographic characteristics and type of health facility (HF). Results: Of 3481 cases of EVD, 579 (16.6%) were nosocomial. Of these, 332 cases occurred in women (57.3%). Patients and visitors accounted for 419 cases (72.4%), of which 79 (18.9%) were aged 6–≤18 years and 108 (25.8%) were aged ≤5 years. Health workers (HWs) accounted for the remaining 160 (27.6%) nosocomial cases. The case fatality rate (CFR) for HWs (66/160, 41.3%) was significantly lower than the CFR for patients and visitors (292/419, 69.7%) (P39 beds) had the highest prevalence of nosocomial EVD (148/579, 25.6%). Among HFs with at least one case of nosocomial infection, 50.0% (98/196) were privately owned. Conclusions: Nurses and traditional healers should be targeted for infection prevention and control training, and supportive supervision should be provided to HFs to mitigate EVD transmission.

Nearly all cases of melioidosis in the continental United States are related to international travel to areas to which Burkholderia pseudomallei, the bacterium that causes melioidosis, is endemic. We report the diagnosis and clinical course of melioidosis in a patient from the United States who had no international travel history and the public health investigation to determine the source of exposure. We tested environmental samples collected from the patient’s home for B. pseudomallei by PCR and culture. Whole-genome sequencing was conducted on PCR-positive environmental samples, and results were compared with sequences from the patient’s clinical specimen. Three PCR-positive environmental samples, all collected from a freshwater home aquarium that had contained imported tropical fish, were a genetic match to the clinical isolate from the patient. This finding suggests a novel route of exposure and a potential for importation of B. pseudomallei, a select agent, into the United States from disease-endemic areas.

We report an analysis of the genomic diversity of isolates of Burkholderia pseudomallei, the cause of melioidosis, recovered in Colombia from routine surveillance during 2016–2017. B. pseudomallei appears genetically diverse, suggesting it is well established and has spread across the region.

To our knowledge, environmental isolation of Burkholderia pseudomallei, the causative agent of melioidosis, from the continental United States has not been reported. We report a case of melioidosis in a Texas resident. Genomic analysis indicated that the isolate groups with B. pseudomallei isolates from patients in the same region, suggesting possible endemicity to this region.

We report 2 cases of melioidosis in women with diabetes admitted to an emergency department in the US Virgin Islands during October 2017. These cases emerged after Hurricanes Irma and Maria and did not have a definitively identified source. Poor outcomes were observed when septicemia and pulmonary involvement were present.

Bacillus anthracis was identified in a 61-year-old man hospitalized in Minnesota, USA. Cooperation between the hospital and the state health agency enhanced prompt identification of the pathogen. Treatment comprising antimicrobial drugs, anthrax immune globulin, and pleural drainage led to full recovery; however, the role of passive immunization in anthrax treatment requires further evaluation.

Burkholderia pseudomallei, the causative agent of melioidosis, was isolated from abscesses of 2 pet green iguanas in California, USA. The international trade in iguanas may contribute to importation of this pathogen into countries where it is not endemic and put persons exposed to these animals at risk for infection.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.

Burkholderia pseudomallei is a bacterium endemic to Southeast Asia and northern Australia, but it has not been found to occur endemically in the United States. We report an ostensibly autochthonous case of melioidosis in the United States. Despite an extensive investigation, the source of exposure was not identified.

We report transmission of Blastomyces dermatitidis fungal infection from a pet kinkajou to a man. When treating a patient with a recalcitrant infection and a history of an animal bite, early and complete animal necropsy and consideration of nonbacterial etiologies are needed.

The US Public Health Emergency Medical Countermeasures Enterprise convened subject matter experts at the 2010 HHS Burkholderia Workshop to develop consensus recommendations for postexposure prophylaxis against and treatment for Burkholderia pseudomallei and B. mallei infections, which cause melioidosis and glanders, respectively. Drugs recommended by consensus of the participants are ceftazidime or meropenem for initial intensive therapy, and trimethoprim/sulfamethoxazole or amoxicillin/clavulanic acid for eradication therapy. For postexposure prophylaxis, recommended drugs are trimethoprim/sulfamethoxazole or co-amoxiclav. To improve the timely diagnosis of melioidosis and glanders, further development and wide distribution of rapid diagnostic assays were also recommended. Standardized animal models and B. pseudomallei strains are needed for further development of therapeutic options. Training for laboratory technicians and physicians would facilitate better diagnosis and treatment options.

BackgroundAcute febrile illness (AFI), a common reason for people seeking medical care globally, represents a spectrum of infectious disease etiologies with important variations geographically and by population. There is no standardized approach to conducting AFI etiologic investigations, limiting interpretation of data in a global context. We conducted a scoping review to characterize current AFI research methodologies, identify global research gaps, and provide methodological research standardization recommendations.Methodology/findingsUsing pre-defined terms, we searched Medline, Embase, and Global Health, for publications from January 1, 2005-December 31, 2017. Publications cited in previously published systematic reviews and an online study repository of non-malarial febrile illness etiologies were also included. We screened abstracts for publications reporting on human infectious disease, aimed at determining AFI etiology using laboratory diagnostics. One-hundred ninety publications underwent full-text review, using a standardized tool to collect data on study characteristics, methodology, and laboratory diagnostics. AFI case definitions between publications varied: use of self-reported fever as part of case definitions (28%, 53/190), fever cut-off value (38·0°C most commonly used: 45%, 85/190), and fever measurement site (axillary most commonly used: 19%, 36/190). Eighty-nine publications (47%) did not include exclusion criteria, and inclusion criteria in 13% (24/190) of publications did not include age group. No publications included study settings in Southern Africa, Micronesia & Polynesia, or Central Asia. We summarized standardized reporting practices, specific to AFI etiologic investigations that would increase inter-study comparability.ConclusionsWider implementation of standardized AFI reporting methods, with multi-pathogen disease detection, could improve comparability of study findings, knowledge of the range of AFI etiologies, and their contributions to the global AFI burden. These steps can guide resource allocation, strengthen outbreak detection and response, target prevention efforts, and improve clinical care, especially in resource-limited settings where disease control often relies on empiric treatment. PROSPERO: CRD42016035666.

Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and no previous history of disease. Diagnosis of the case was confirmed through multiple microbiologic and molecular techniques. To enhance the epidemiological analysis, we conducted several molecular genotyping procedures, including multi-locus sequence typing, SNP-profiling, and whole genome sequence typing. Each technique has different molecular epidemiologic advantages, all of which provided evidence that the infecting strain was most similar to those found in Southeast Asia, possibly originating in, or around, Malaysia. Advancements in new typing technologies provide genotyping resolution not previously available to public health investigators, allowing for more accurate source identification.

Introduction: The purpose of this review is to examine African Ebola outbreaks from their first discovery to the present, to determine how the medical and public health response has changed and identify the causes for those changes. We sought to describe what is now known about the epidemiology and spread of Ebola virus disease (EVD) from the significant outbreaks that have occurred and outbreak control methods applied under often challenging circumstances. Given the substantial role that the U.S. Government and the U.S. DoD have played in the 2014 to 2016 West African Ebola outbreak, the role of the DoD and the U.S. Africa Command in controlling EVD is described., Materials and Methods: A descriptive method design was used to collect and analyze all available Ebola outbreak literature using the PubMed database. An initial literature search was conducted by searching for, obtaining, and reading original source articles on all major global Ebola outbreaks. To conduct a focused search, we used initial search terms "Ebola outbreak," "Ebola virus disease," "Ebola response," "Ebola countermeasures," and also included each country's name where Ebola cases are known to have occurred. From the 4,673 unique articles obtained from this search and subsequent article title review, 307 articles were identified for potential inclusion. Following abstract and article review, 45 original source articles were used to compile the history of significant Ebola outbreaks. From this compilation, articles focused on each respective subsection of this review to delineate and describe the history of EVD and response, identifying fundamental changes, were obtained and incorporated., Results: We present known Ebola virus and disease attributes, including a general description, seasonality and location, transmission capacity, clinical symptoms, surveillance, virology, historical EVD outbreaks and response, international support for Ebola outbreak response, U.S. DoD support, medical countermeasures supporting outbreak response, remaining gaps to include policy limitations, regional instability, climate change, migration, and urbanization, public health education and infrastructure, and virus persistence and public awareness., Conclusions: The health and societal impacts of EVD on Africa has been far-reaching, with about 35,000 cases and over 15,000 deaths, with small numbers of cases spreading globally. However, the history of combatting EVD reveals that there is considerable hope for African nations to quickly and successfully respond to Ebola outbreaks, through use of endemic resources including Africa CDC and African Partner Outbreak Response Alliance and the U.S. Africa Command with greater DoD reachback. Although there remains much to be learned about the Ebola virus and EVD including whether the potential for novel strains to become deadly emerging infections, invaluable vaccines, antivirals, and public health measures are now part of the resources that can be used to combat this disease., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: The Leprosy Post-Exposure Prophylaxis (LPEP) program explored the feasibility and impact of contact tracing and the provision of single dose rifampicin (SDR) to eligible contacts of newly diagnosed leprosy patients in Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. As the impact of the programme is difficult to establish in the short term, we apply mathematical modelling to predict its long-term impact on the leprosy incidence., Methodology: The individual-based model SIMCOLEP was calibrated and validated to the historic leprosy incidence data in the study areas. For each area, we assessed two scenarios: 1) continuation of existing routine activities as in 2014; and 2) routine activities combined with LPEP starting in 2015. The number of contacts per index patient screened varied from 1 to 36 between areas. Projections were made until 2040., Principal Findings: In all areas, the LPEP program increased the number of detected cases in the first year(s) of the programme as compared to the routine programme, followed by a faster reduction afterwards with increasing benefit over time. LPEP could accelerate the reduction of the leprosy incidence by up to six years as compared to the routine programme. The impact of LPEP varied by area due to differences in the number of contacts per index patient included and differences in leprosy epidemiology and routine control programme., Conclusions: The LPEP program contributes significantly to the reduction of the leprosy incidence and could potentially accelerate the interruption of transmission. It would be advisable to include contact tracing/screening and SDR in routine leprosy programmes., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Novartis Foundation and International Federation of Anti-Leprosy Association partners provided technical input in the design phase of the LPEP program and ensured overall programme coordination. All authors are either staff of the Novartis Foundation (Arielle Cavaliero, Zaahira Gani, and Ann Aerts), work as paid consultants for the programme described here (David J Blok, Peter Steinmann, Anuj Tiwari, Tanja Barth-Jaeggi, Marc Bonenberger, Helena Grete, Christa Kasang, Liesbeth Mieras, Unnati R Saha, Wim H van Brakel, Bart Vander Plaetse, and Jan Hendrik Richardus), act as national programme coordinators (Mohammad A Arif, Nand Lal Banstola, Rabindra Baskota, Teky Budiawan, Eliane Ignotti, Deusdedit V Kamara, Pratap R Manglani, Blasdus F Njako, Tiara Pakasi, Nayani D Suriyarachchi, Aye Tin Maung, Tin Shwe, and Millawage S D Wijesinghe) or serve on the Steering Committee of the programme (David Blaney, Paul Saunderson, W Cairns S Smith, René Stäheli, Jan van Berkel, Marcos Virmond). The funder had no role in the interpretation of findings or decision to publish this manuscript. Author Aye Tin Maung was unavailable to confirm his authorship contributions. On his behalf, the corresponding author has reported his contributions to the best of his knowledge.

Background: Innovative approaches are required for leprosy control to reduce cases and curb transmission of Mycobacterium leprae. Early case detection, contact screening, and chemoprophylaxis are the most promising tools. We aimed to generate evidence on the feasibility of integrating contact tracing and administration of single-dose rifampicin (SDR) into routine leprosy control activities., Methods: The leprosy post-exposure prophylaxis (LPEP) programme was an international, multicentre feasibility study implemented within the leprosy control programmes of Brazil, India, Indonesia, Myanmar, Nepal, Sri Lanka, and Tanzania. LPEP explored the feasibility of combining three key interventions: systematically tracing contacts of individuals newly diagnosed with leprosy; screening the traced contacts for leprosy; and administering SDR to eligible contacts. Outcomes were assessed in terms of number of contacts traced, screened, and SDR administration rates., Findings: Between Jan 1, 2015, and Aug 1, 2019, LPEP enrolled 9170 index patients and listed 179 769 contacts, of whom 174 782 (97·2%) were successfully traced and screened. Of those screened, 22 854 (13·1%) were excluded from SDR mainly because of health reasons and age. Among those excluded, 810 were confirmed as new patients (46 per 10 000 contacts screened). Among the eligible screened contacts, 1182 (0·7%) refused prophylactic treatment with SDR. Overall, SDR was administered to 151 928 (86·9%) screened contacts. No serious adverse events were reported., Interpretation: Post-exposure prophylaxis with SDR is safe; can be integrated into different leprosy control programmes with minimal additional efforts once contact tracing has been established; and is generally well accepted by index patients, their contacts, and health-care workers. The programme has also invigorated local leprosy control through the availability of a prophylactic intervention; therefore, we recommend rolling out SDR in all settings where contact tracing and screening have been established., Funding: Novartis Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Innovative approaches are required to further enhance leprosy control, reduce the number of people developing leprosy, and curb transmission. Early case detection, contact screening, and chemoprophylaxis currently is the most promising approach to achieve this goal. The Leprosy Post-Exposure Prophylaxis (LPEP) programme generates evidence on the feasibility of integrating contact tracing and single-dose rifampicin (SDR) administration into routine leprosy control activities in different settings. The LPEP programme is implemented within the leprosy control programmes of Brazil, Cambodia, India, Indonesia, Myanmar, Nepal, Sri Lanka and Tanzania. Focus is on three key interventions: tracing the contacts of newly diagnosed leprosy patients; screening the contacts for leprosy; and administering SDR to eligible contacts. Country-specific protocol adaptations refer to contact definition, minimal age for SDR, and staff involved. Central coordination, detailed documentation and rigorous supervision ensure quality evidence. Around 2 years of field work had been completed in seven countries by July 2017. The 5,941 enrolled index patients (89·4% of the registered) identified a total of 123,311 contacts, of which 99·1% were traced and screened. Among them, 406 new leprosy patients were identified (329/100,000), and 10,883 (8·9%) were excluded from SDR for various reasons. Also, 785 contacts (0·7%) refused the prophylactic treatment with SDR. Overall, SDR was administered to 89·0% of the listed contacts. Post-exposure prophylaxis with SDR is safe; can be integrated into the routines of different leprosy control programmes; and is generally well accepted by index patients, their contacts and the health workforce. The programme has also invigorated local leprosy control., Competing Interests: Conflicts of interest Novartis Foundation provided technical input in the design phase of the LPEP programme and ensures overall programme coordination. All authors are either staff of the Novartis Foundation, work as paid consultants for the programme described here, act as national programme coordinators or serve on the Steering Committee of the programme. The funder had no role in the interpretation of findings or decision to publish this manuscript.

Hansen's disease (HD), or leprosy, is caused by the bacterium Mycobacterium leprae and is reportable in many states. It is a chronic disease affecting the skin and nerves, commonly presenting as pale or reddish skin patches with diminished sensation. Without treatment, it can progress to a severely debilitating disease with nerve damage, tissue destruction, and functional loss. An important factor in limiting HD morbidity is early diagnosis and prompt initiation of therapy. Because HD is rare, clinicians in the United States are often unfamiliar with it; however, HD continues to cause morbidity in the United States. To better characterize at-risk U.S. populations, HD trends during 1994-2011 were evaluated by reviewing records from the National Hansen's Disease Program (NHDP). When the periods 1994-1996 and 2009-2011 were compared, a decline in the rate for new diagnoses from 0.52 to 0.43 per million was observed. The rate among foreign-born persons decreased from 3.66 to 2.29, whereas the rate among U.S.-born persons was 0.16 in both 1994-1996 and 2009-2011. Delayed diagnosis was more common among foreign-born persons. Clinicians throughout the United States should familiarize themselves with the signs and symptoms of HD and understand that HD can occur in the 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.

Identification of the select agent Burkholderia pseudomallei in macaques imported into the United States is rare. A purpose-bred, 4.5-y-old pigtail macaque (Macaca nemestrina) imported from Southeast Asia was received from a commercial vendor at our facility in March 2012. After the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. The wound was treated and resolved over 3 mo. In August 2012, 2 mo after the stifle joint wound resolved, the macaque exhibited neurologic clinical signs. Postmortem microbiologic analysis revealed that the macaque was infected with B. pseudomallei. This case report describes the clinical evaluation of a B. pseudomallei-infected macaque, management and care of the potentially exposed colony of animals, and protocols established for the animal care staff that worked with the infected macaque and potentially exposed colony. This article also provides relevant information on addressing matters related to regulatory issues and risk management of potentially exposed animals and animal care staff.

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, is endemic to Southeast Asia and northern Australia but is only very rarely seen in patients in the United States. We report pulmonary B pseudomallei infection in a young girl with cystic fibrosis (CF) who had never traveled to Asia or Australia. Biochemical and epidemiologic investigation determined Aruba as the likely site of disease acquisition. This report highlights the ability of patients with CF to acquire this organism outside of Southeast Asia and describes an aggressive treatment regimen that has kept this patient culture-negative for the organism over a long period of time.

Background: The aim of appraisal is to provide an opportunity for individuals to reflect on their work to facilitate learning and development. Appraisal for GPs has been a contractual requirement since 2004 in Scotland, and is seen as an integral part of revalidation., Aim: To investigate the outcomes of GP appraisal in terms of whether it has prompted change in medical practice, education and learning, career development, attitudes to health and probity, how GPs organise their work, and their perception of the overall value of the process., Design of Study: A cross-sectional postal questionnaire., Setting: GP performers in Scotland who had undertaken appraisal., Method: The questionnaire was based on the seven principles outlined in Good Medical Practice, a literature review, and previous local research. The survey was conducted on a strictly anonymous basis with a random, representative sample of GPs., Results: Fifty-three per cent (671/1278) responded. Forty-seven per cent (308/661) thought that appraisal had altered their educational activity, 33% (217/660) reported undertaking further education or training as a result of appraisal, and 13% (89/660) felt that appraisal had influenced their career development. Opinion was evenly split on the overall value of appraisal., Conclusion: Appraisal can have a significant impact on all aspects of a GP's professional life, and those who value the process report continuing benefit in how they manage their education and professional development. However, many perceive limited or no benefit. The renewed emphasis on appraisal requires examination of these findings and discussion of how appraisal can become more relevant.

Objective: The purpose of this study was to determine whether patient ratings of general practice Registrars' consulting skills are associated with 'expert' scoring using the MRCGP video assessment protocol., Methods: A cross-sectional observational study of general practice Registrars' consultation skills was carried out in 23 practices in South East Scotland using two types of patient assessment compared with expert assessment of video consultation. The main outcome measures were rank correlation of Registrars' overall level of attainment on the Royal College of General Practitioner (RCGP) video assessment with mean score on the Patient Enablement Instrument (PEI) and mean score on the Consultation Satisfaction Questionnaire (CSQ)., Results: The rank correlation of Registrars' mean PEI scores with marks on the RCGP video component was 0.01 (P = 0.97, n = 19) and mean CSQ score 0.05 (P = 0.83, n = 19). There were no adverse comments from patients, but Registrars and trainers found the process onerous., Conclusion: No meaningful association was identified between Registrars' score on the RCGP video examination and patient assessment via either the PEI or the CSQ. This suggests that, with regard to measuring quality in the consultation, one or more of the assessments are invalid or that they are measuring different attributes. Further research to elucidate the reasons for the lack of correlation is required.