Mpox: The Reemergence of an Old Disease and Inequities.

Mpox, previously known as monkeypox, is caused by an Orthopoxvirus related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.

What's Hot This Year in Infectious Diseases Clinical Science.

The field of infectious diseases saw numerous exciting advances in 2023. Trials of new antibiotics and treatment regimens sought to address rising rates of antimicrobial resistance. Other studies focused on the most appropriate use of currently available treatments, balancing the dual goals of providing effective treatment and impactful antimicrobial stewardship. Improvements in disease prevention were made through trials of both new vaccines and new chemoprophylaxis approaches. Concerning trends this year included increasing rates of invasive group A streptococcal infections, medical tourism-associated cases of fungal meningitis, and the return of locally acquired malaria to the United States. This review covers some of these notable trials and clinical developments in infectious diseases in the past year.

Emerging Enterovirus A71 Subgenogroup B5 Causing Severe Hand, Foot, and Mouth Disease, Vietnam, 2023.

We report on a 2023 outbreak of severe hand, foot, and mouth disease in southern Vietnam caused by an emerging lineage of enterovirus A71 subgenogroup B5. Affected children were significantly older than those reported during previous outbreaks. The virus should be closely monitored to assess its potential for global dispersal.

Zoonotic and Zooanthroponotic Potential of Monkeypox.

The current multicounty outbreak of monkeypox virus (MPXV) posed an emerging and continued challenge to already strained public healthcare sector, around the globe. Since its first identification, monkeypox disease (mpox) remained enzootic in Central and West African countries where reports of human cases are sporadically described. Recent trends in mpox spread outside the Africa have highlighted increased incidence of spillover of the MPXV from animal to humans. While nature of established animal reservoirs remained undefined, several small mammals including rodents, carnivores, lagomorphs, insectivores, non-human primates, domestic/farm animals, and several species of wildlife are proposed to be carrier of the MPXV infection. There are established records of animal-to-human (zoonotic) spread of MPXV through close interaction of humans with animals by eating bushmeat, contracting bodily fluids or trading possibly infected animals. In contrast, there are reports and increasing possibilities of human-to-animal (zooanthroponotic) spread of the MPXV through petting and close interaction with pet owners and animal care workers. We describe here the rationales and molecular factors which predispose the spread of MPXV not only amongst humans but also from animals to humans. A range of continuing opportunities for the spread and evolution of MPXV are discussed to consider risks beyond the currently identified groups. With the possibility of MPXV establishing itself in animal reservoirs, continued and broad surveillance, investigation into unconventional transmissions, and exploration of spillover events are warranted.

Using Serum Specimens for Real-Time PCR-Based Diagnosis of Human Granulocytic Anaplasmosis, Canada.

Whole blood is the optimal specimen for anaplasmosis diagnosis but might not be available in all cases. We PCR tested serum samples collected in Canada for Anaplasma serology and found 84.8%-95.8% sensitivity and 2.8 average cycle threshold elevation. Serum can be acceptable for detecting Anaplasma spp. when whole blood is unavailable.

Powassan Virus Infection Detected by Metagenomic Next-Generation Sequencing, Ohio, USA.

We describe a 4-year-old male patient in Ohio, USA, who had encephalitis caused by Powassan virus lineage 2. Virus was detected by using metagenomic next-generation sequencing and confirmed with IgM and plaque reduction neutralization assays. Clinicians should recognize changing epidemiology of tickborne viruses to enhance encephalitis diagnosis and management.

Fatal Case of Heartland Virus Disease Acquired in the Mid-Atlantic Region, United States.

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Flaviviruses and the Traveler: Around the World and to Your Stage. A Review of West Nile, Yellow Fever, Dengue, and Zika Viruses for the Practicing Pathologist.

Flaviviruses are a genus of single-stranded RNA viruses that impose an important and growing burden to human health. There are over 3 billion individuals living in areas where flaviviruses are endemic. Flaviviruses and their arthropod vectors (which include mosquitoes and ticks) take advantage of global travel to expand their distribution and cause severe disease in humans, and they can be grouped according to their vector and pathogenicity. The mosquito-borne flaviviruses cause a spectrum of diseases from encephalitis to hepatitis and vascular shock syndrome, congenital abnormalities, and fetal death. Neurotropic infections such as Zika virus and West Nile virus cross the blood-brain barrier and infect neurons and other cells, leading to meningoencephalitis. In the hemorrhagic fever clade, there are yellow fever virus, the prototypical hemorrhagic fever virus that infects hepatocytes, and dengue virus, which infects cells of the reticuloendothelial system and can lead to a dramatic plasma cell leakage and shock syndrome. Zika virus also causes congenital infections and fetal death and is the first and only example of a teratogenic arbovirus in humans. Diagnostic testing for flaviviruses broadly includes the detection of viral RNA in serum (particularly within the first 10 days of symptoms), viral isolation by cell culture (rarely performed due to complexity and biosafety concerns), and histopathologic evaluation with immunohistochemistry and molecular testing on formalin-fixed paraffin-embedded tissue blocks. This review focuses on 4 mosquito-borne flaviviruses-West Nile, yellow fever, dengue, and Zika virus-and discusses the mechanisms of transmission, the role of travel in geographic distribution and epidemic emergence, and the clinical and histopathologic features of each. Finally, prevention strategies such as vector control and vaccination are discussed.

One Health: The Role of Pathology as it Pertains to Diagnosis of Zoonoses and Discovery of Emerging Infections.

Pathologists are an integral part of One Health as they are a critical component of the multidisciplinary team that diagnoses zoonotic diseases and discovers emerging pathogens. Both human and veterinary pathologists are uniquely positioned to identify clusters or trends in patient populations that can be caused by an infectious agent and preface emerging outbreaks. The repository of tissue samples available to pathologists is an invaluable resource that can be used to investigate a variety of pathogens. One Health is an encompassing approach that focuses on optimizing the health of humans, animals (domesticated and sylvatic), and the ecosystem, including plants, water, and vectors. In this integrated and balanced approach, multiple disciplines and sectors from local and global communities work together to promote overall well-being of the 3 components and address threats such as emerging infectious diseases and zoonoses. Zoonoses are defined as infectious diseases that are spread between animals and humans through different mechanisms, including direct contact, food, water, vectors, or fomites. This review highlights examples in which human and veterinary pathologists were an integral part of the multisectoral team that identified uncommon etiologic agents or pathologies that had not been elucidated clinically. As the team discovers an emerging infectious disease, pathologists develop and validate tests for epidemiologic and clinical use and provide surveillance data on these diseases. They define the pathogenesis and pathology that these new diseases cause. This review also presents examples that demonstrate the crucial role pathologists play in diagnosing zoonoses that have an impact on the food supply and the economy.

PHYSICIANS' MORAL DUTIES DURING PANDEMICS.

BACKGROUND: Pandemics with devastating morbidity and mortality have occurred repeatedly throughout recorded history. Each new scourge seems to surprise governments, medical experts, and the public. The SARS CoV-2 (COVID-19) pandemic, for example, arrived as an unwelcome surprise to an unprepared world. DISCUSSION: Despite humanity's extensive experience with pandemics and their associated ethical dilemmas, no consensus has emerged on preferred normative standards to deal with them. In this article, we consider the ethical dilemmas faced by physicians who work in these risk-prone situations and propose a set of ethical norms for current and future pandemics. As front-line clinicians for critically ill patients during pandemics, emergency physicians will play a substantial role in making and implementing treatment allocation decisions. CONCLUSION: Our proposed ethical norms should help future physicians make morally challenging choices during pandemics.

Pathology and Pathogenesis of Lassa Fever: Novel Immunohistochemical Findings in Fatal Cases and Clinico-pathologic Correlation.

BACKGROUND: Lassa fever is a zoonotic, acute viral illness first identified in Nigeria in 1969. An estimate shows that the "at risk" seronegative population (in Sierra Leone, Guinea, and Nigeria) may be as high as 59 million, with an annual incidence of all illnesses of 3 million, and fatalities up to 67 000, demonstrating the serious impact of the disease on the region and global health. METHODS: Histopathologic evaluation, immunohistochemical assay, and electron microscopic examination were performed on postmortem tissue samples from 12 confirmed Lassa fever cases. RESULTS: Lassa fever virus antigens and viral particles were observed in multiple organ systems and cells, including cells in the mononuclear phagocytic system and other specialized cells where it had not been described previously. CONCLUSIONS: The immunolocalization of Lassa fever virus antigens in fatal cases provides novel insightful information with clinical and pathogenetic implications. The extensive involvement of the mononuclear phagocytic system, including tissue macrophages and endothelial cells, suggests participation of inflammatory mediators from this lineage with the resulting vascular dilatation and increasing permeability. Other findings indicate the pathogenesis of Lassa fever is multifactorial and additional studies are needed.

Novel Hendra Virus Variant Circulating in Black Flying Foxes and Grey-Headed Flying Foxes, Australia.

A novel Hendra virus variant, genotype 2, was recently discovered in a horse that died after acute illness and in Pteropus flying fox tissues in Australia. We detected the variant in flying fox urine, the pathway relevant for spillover, supporting an expanded geographic range of Hendra virus risk to horses and humans.

Evidence of Prolonged Crimean-Congo Hemorrhagic Fever Virus Endemicity by Retrospective Serosurvey, Eastern Spain.

We conducted a retrospective serosurvey for antibodies against Crimean-Congo hemorrhagic fever virus in wild ungulates along the eastern Mediterranean Coast of Spain. The virus has been endemic in this region since 2010 but is mainly restricted to geographic clusters with extremely high seropositivity associated with high density of bovids.

A Review of the Ring Trial Design for Evaluating Ring Interventions for Infectious Diseases.

In trials of infectious disease interventions, rare outcomes and unpredictable spatiotemporal variation can introduce bias, reduce statistical power, and prevent conclusive inferences. Spillover effects can complicate inference if individual randomization is used to gain efficiency. Ring trials are a type of cluster-randomized trial that may increase efficiency and minimize bias, particularly in emergency and elimination settings with strong clustering of infection. They can be used to evaluate ring interventions, which are delivered to individuals in proximity to or contact with index cases. We conducted a systematic review of ring trials, compare them with other trial designs for evaluating ring interventions, and describe strengths and weaknesses of each design. Of 849 articles and 322 protocols screened, we identified 26 ring trials, 15 cluster-randomized trials, 5 trials that randomized households or individuals within rings, and 1 individually randomized trial. The most common interventions were postexposure prophylaxis (n = 23) and focal mass drug administration and screening and treatment (n = 7). Ring trials require robust surveillance systems and contact tracing for directly transmitted diseases. For rare diseases with strong spatiotemporal clustering, they may have higher efficiency and internal validity than cluster-randomized designs, in part because they ensure that no clusters are excluded from analysis due to zero cluster incidence. Though more research is needed to compare them with other types of trials, ring trials hold promise as a design that can increase trial speed and efficiency while reducing bias.

Epidemiologic features, clinical characteristics, and predictors of mortality in patients with candidemia in Alameda County, California; a 2017-2020 retrospective analysis.

BACKGROUND: Bloodstream infections caused by Candida species are responsible for significant morbidity and mortality worldwide, with an ever-changing epidemiology. We conducted this study to assess trends in the epidemiologic features, risk factors and Candida species distribution in candidemia patients in Alameda County, California. METHODS: We analyzed data collected from patients in Alameda County, California between 2017 and 2020 as part of the California Emerging Infections Program (CEIP). This is a laboratory-based, active surveillance program for candidemia. In our study, we included incident cases only. RESULTS: During the 4-year period from January 1st, 2017, to December 31st, 2020, 392 incident cases of candidemia were identified. The mean crude annual cumulative incidence was 5.9 cases per 100,000 inhabitants (range 5.0-6.5 cases per 100,000 population). Candida glabrata was the most common Candida species and was present as the only Candida species in 149 cases (38.0%), followed by Candida albicans, 130 (33.2%). Mixed Candida species were present in 13 patients (3.3%). Most of the cases of candidemia occurred in individuals with one or more underlying conditions. Multivariate regression models showed that age ≥ 65 years (RR 1.66, CI 1.28-2.14), prior administration of systemic antibiotic therapy, (RR 1.84, CI 1.06-3.17), cirrhosis of the liver, (RR 2.01, CI 1.51-2.68), and prior admission to the ICU (RR1.82, CI 1.36-2.43) were significant predictors of mortality. CONCLUSIONS: Non-albicans Candida species currently account for the majority of candidemia cases in Alameda County.

Household transmission of the Delta COVID-19 variant in Queensland, Australia: a case series.

Household transmission plays a key role in the spread of COVID-19 through populations. In this paper, we report on the transmission of COVID-19 within households in a metropolitan area in Australia, examine the impact of various factors and highlight priority areas for future public health responses. We collected and reviewed retrospective case report data and follow-up interview responses from households with a positive case of the Delta COVID-19 variant in Queensland in 2021. The overall secondary attack rate (SAR) among household contacts was 29.6% and the mean incubation period for secondary cases was 4.3 days. SAR was higher where the index case was male (57.9% vs. 14.3%) or aged ≤12 years (38.7% vs. 17.4%) but similar for adult contacts that were double vaccinated (35.7%) and unvaccinated (33.3%). Most interview participants emphasised the importance of clear, consistent and compassionate health advice as a key priority for managing outbreaks in the home. The overall rate of household transmission was slightly higher than that reported in previous studies on the wild COVID-19 variant and secondary infections developed more rapidly. While vaccination did not appear to affect the risk of transmission to adult subjects, uptake in the sample was ultimately high.

Blastomycosis in Africa and the Middle East: A Comprehensive Review of Reported Cases and Reanalysis of Historical Isolates Based on Molecular Data.

BACKGROUND: Blastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in North America and caused by Blastomyces dermatitidis and Blastomyces gilchristii. METHODS: We reviewed published cases of human and veterinary blastomycosis from Africa and the Middle East. We abstracted epidemiological and clinical features of cases, including sites of disease, diagnosis, management, outcomes, and, where available, genetic and antigenic typing of case isolates. In addition, we sequenced nucleic acids from 9 clinical isolates from Africa deposited in global collections as B. dermatitidis; for 5, we sequenced the internal transcribed spacer regions, and for the other 4 we sequenced the whole genomes. RESULTS: We identified 172 unique human patients with blastomycosis, including 159 patients from 25 African countries and 12 patients from 5 Middle Eastern countries, and also identified 7 reports of veterinary blastomycosis. In humans, cutaneous disease predominated (n = 100/137, 73%), followed by pulmonary (n = 73/129, 57%) and osteoarticular involvement (n = 61/128, 48%). Unusual direct microscopy/histopathological presentations included short hyphal fragments in tissues (n = 23/129, 18%). There were 34 genotyped case isolates that comprised 4 species: Blastomyces percursus (n = 22, 65%), from 8 countries throughout all regions; Blastomyces emzantsi (n = 9, 26%), from South Africa; B. dermatitidis (n = 1, 3%), from the Democratic Republic of Congo; and B. gilchristii (n = 2, 6%), from South Africa and Zimbabwe. CONCLUSIONS: Blastomycosis occurs throughout Africa and the Middle East and is caused predominantly by B. percursus and, at least in South Africa, B. emzantsi, resulting in distinct clinical and pathological patterns of disease.

Universal Admission Screening for SARS-CoV-2 Infections among Hospitalized Patients, Switzerland, 2020.

Switzerland began a national lockdown on March 16, 2020, in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the prevalence of SARS-CoV-2 infection among patients admitted to 4 hospitals in the canton of Zurich, Switzerland, in April 2020. These 4 acute care hospitals screened 2,807 patients, including 2,278 (81.2%) who did not have symptoms of coronavirus disease (COVID-19). Overall, 529 (18.8%) persons had >1 symptom of COVID-19, of whom 60 (11.3%) tested positive for SARS-CoV-2. Eight asymptomatic persons (0.4%) also tested positive for SARS-CoV-2. Our findings indicate that screening on the basis of COVID-19 symptoms, regardless of clinical suspicion, can identify most SARS-CoV-2-positive persons in a low-prevalence setting.

Epidemiological investigation of recurrent outbreaks of haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli serotype O55:H7 in England, 2014-2018.

Recurrent outbreaks of haemolytic uraemic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC) serotype O55:H7 occurred in England between 2014 and 2018. We reviewed the epidemiological evidence to identify potential source(s) and transmission routes of the pathogen, and to assess the on-going risk to public health. Over the 5-year period, there were 43 confirmed and three probable cases of STEC O55:H7. The median age of cases was 4 years old (range 6 months to 69 years old) and over half of all cases were female (28/46, 61%). There were 36/46 (78.3%) symptomatic cases, and over half of all cases developed HUS (25/46, 54%), including two fatal cases. No common food or environmental exposures were identified, although the majority of cases lived in rural or semi-rural environments and reported contact with both wild and domestic animals. This investigation informed policy on the clinical and public health management of HUS caused by STEC other than serotype O157:H7 (non-O157 STEC) in England, including comprehensive testing of all household contacts and household pets and more widespread use of polymerase chain reaction assays for the rapid diagnosis of STEC-HUS.

Hospital Readmissions After Laboratory-Confirmed Influenza Hospitalization.

BACKGROUND: Influenza infection causes substantial morbidity and mortality. However, little is known about hospital readmissions after an influenza hospitalization. The aim of our study was to characterize frequency of hospital readmissions among patients hospitalized with laboratory-confirmed influenza. METHODS: We conducted a retrospective study using Tennessee Emerging Infections Program Influenza Surveillance data from 2006 to 2016 and the concurrent Tennessee Hospital Discharge Data System. We analyzed demographic characteristics and outcomes to better understand frequency and factors associated with hospital readmissions. RESULTS: Of the 2897 patients with a laboratory-confirmed influenza hospitalization, 409 (14%) and 1364 (47%) had at least 1 hospital readmission within 30 days and 1 year of the influenza hospitalization, respectively. Multiple readmissions occurred in 739 patients (54%). The readmission group was older, female predominant, and had more comorbidities than patients not hospitalized. Pneumonia, acute chronic obstructive pulmonary disease/asthma exacerbation, septicemia, acute respiratory failure, and acute renal failure were the most common causes for readmission at 30 days. Underlying cardiovascular disease, lung disease, kidney disease, diabetes, immunosuppression, and liver disease were associated with increased risk of readmission during the subsequent year. CONCLUSIONS: After an admission with laboratory-confirmed influenza, there is a high likelihood of readmission within 30 days and 1 year adding to the morbidity of influenza.