Contemporary Outbreaks Research Articles

Происхождение политической эсхатологии в Европе: Французская революция как космическая борьба добрых и злых сил

Eschatology is a religious doctrine about the coming end of the world and the coming of a new age. Beginning in the late 18th century, eschatology acquired a political content and was used often by many European ideologies, especially nationalism and socialism, to explain the course of history. Revolutions often included an eschatological content. The French Revolution was the first major European revolution with a large eschatological content. This article examines the influence of eschatology on the course of this revolution. The eschatological tendencies, begun in the French and other revolutions, culminated in the Russian Revolution of 1917-1922. These tendencies included dividing people into categories of the saved and condemned, demonization of enemies, especially internal ones, conspiracy theories, compiling criteria for membership in a political or ethnic nation, determining norms of correct behavior for members of the nation, compiling criteria for the exclusion of people from the ranks of the nation. The article theme has a certain relevance to contemporary outbreaks of political and religious eschatology in different movements and ideologies.

Eat, Drink, and Be Merry: coping with zoonotic spillovers and climate injustice

ABSTRACT This art installation centers on then-recent outbreaks of rabies and Nipah viruses in India and Bangladesh, and reveals unexpected connections between vultures, fruit bats, and humans. Using Victorian and Dutch decorative arts from time periods in which England and the Netherlands were connected to these contemporary outbreak sites through colonization, the installation highlights the way climate injustice influences which humans and animals bear the most risk in disease spillovers. Using work by cultural anthropologist Ernest Becker, the installation also considers how culture (particularly art) functions as a psychological mechanism for coping with death anxiety.

Invasive Species: Immunity and Community in Contemporary Outbreak Narratives

AbstractThe word contagion, derived from Latin contagio, the combination of con (“together with”) and tagio (“touch”), suggests a close relationship between the human body and community. It stands to reason, then, that contagion narratives in one way or the other attempt to reflect upon one’s being in the world, with others, whether human or non‐human, and they do so through the theme of communicable disease and shared physical vulnerability. In the last couple of decades, Russian literature has witnessed an uptick in outbreak narratives fueled by anxieties over globalization and the ever‐shrinking distances and ever‐increasing mobility of our “global village.” The paper analyzes two of such recent novels, Vladimir Sorokin’s The Blizzard (2010) and Eduard Verkin’s Sakhalin Island (2018), to examine whether these developments lead the authors to conceptualize new forms of community and communality or, on the contrary, retreat into nostalgic restoration, nationalism, and tribalism.

Dengue virus M and E proteins belonging to genotype II (Cosmopolitan) of serotype 2 are influenced by the nature of M residue 36.

Mosquito-borne dengue disease is caused by the dengue virus serotype-1 to serotype-4. The contemporary dengue outbreaks in the southwestern Indian ocean coincided with the widespread of dengue virus serotype 2 genotype II (Cosmopolitan), including epidemic viral strains DES-14 and RUN-18 isolated in Dar es Salaam (Tanzania) in 2014 and La Reunion Island (France) in 2018, respectively. Heterodimeric interaction between prM (intracellular precursor of surface structural M protein) and envelope E proteins is required during the initial stage of dengue virus assembly. Amino acid 127 of DES-14 prM protein (equivalent to M36) has been identified as an infrequent valine whereas RUN-18 has a common isoleucine. In the present study, we examined the effect of M-I36V mutation on the expression of a recombinant RUN-18 E protein co-expressed with prM in human epithelial A549 cells. The M ectodomain of dengue virus serotype 2 embeds a pro-apoptotic peptide referred as D2AMP. The impact of M-I36V mutation on the death-promoting capability of D2AMP was assessed in A549 cells. We showed that valine at position M36 affects expression of recombinant RUN-18 E protein and potentiates apoptosis-inducing activity of D2AMP. We propose that the nature of M residue 36 influences the virological characteristics of dengue 2 M and E proteins belonging to genotype II that contributes to global dengue burden.

Examining the Prevailing Negative Sentiments Surrounding Measles Vaccination: Unsupervised Deep Learning of Twitter Posts from 2017 to 2022.

Despite the proven safety and clinical efficacy of the Measles vaccine, many countries are seeing new heights of vaccine hesitancy or refusal, and are experiencing a resurgence of measles infections as a consequence. With the use of novel machine learning tools, we investigated the prevailing negative sentiments related to Measles vaccination through an analysis of public Twitter posts over a 5-year period. We extracted original tweets using the search terms related to "measles" and "vaccine," and posted in English from January 1, 2017, to December 15, 2022. Of these, 155,363 tweets were identified to be negative sentiment tweets from unique individuals, through the use of Bidirectional Encoder Representations from Transformers (BERT) Named Entity Recognition and SieBERT, a pretrained sentiment in English analysis model. This was followed by topic modeling and qualitative thematic analysis performed inductively by the study investigators. A total of 11 topics were generated after applying BERTopic. To facilitate a global discussion of results, the topics were grouped into four different themes through iterative thematic analysis. These include (a) the rejection of "anti-vaxxers" or antivaccine sentiments, (b) misbeliefs and misinformation regarding Measles vaccination, (c) negative transference due to COVID-19 related policies, and (d) public reactions to contemporary Measles outbreaks. Theme 1 highlights that the current public discourse may further alienate those who are vaccine hesitant because of the disparaging language often used, while Themes 2 and 3 highlight the typology of misperceptions and misinformation underlying the negative sentiments related to Measles vaccination and the psychological tendency of disconfirmation bias. Nonetheless, the analysis was based solely on Twitter and only tweets in English were included; hence, the findings may not necessarily generalize to non-Western communities. It is important to further understand the thinking and feeling of those who are vaccine hesitant to address the issues at hand.

Systematic review of global hepatitis E outbreaks to inform response and coordination initiatives

IntroductionHepatitis E virus (HEV) is the most common cause of acute hepatitis. While symptoms are generally mild and resolve within weeks, some populations (e.g., pregnant women, immunocompromised adults) are at high-risk of severe HEV-related morbidity and mortality. There has not been a recent comprehensive review of contemporary HEV outbreaks, which limits the validity of current disease burden estimates. Therefore, we aimed to characterize global HEV outbreaks and describe data gaps to inform HEV outbreak prevention and response initiatives.MethodsWe performed a systematic review of peer-reviewed (PubMed, Embase) and gray literature (ProMED) to identify reports of outbreaks published between 2011 and 2022. We included (1) reports with ≥ 5 cases of HEV, and/or (2) reports with 1.5 times the baseline incidence of HEV in a specific population, and (3) all reports with suspected (e.g., clinical case definition) or confirmed (e.g., ELISA or PCR test) cases if they met criterium 1 and/or 2. We describe key outbreak epidemiological, prevention and response characteristics and major data gaps.ResultsWe identified 907 records from PubMed, 468 from Embase, and 247 from ProMED. We screened 1,362 potentially relevant records after deduplication. Seventy-one reports were synthesized, representing 44 HEV outbreaks in 19 countries. The populations at risk, case fatalities, and outbreak durations were not reported in 66% of outbreak reports. No reports described using HEV vaccines. Reported intervention efforts included improving sanitation and hygiene, contact tracing/case surveillance, chlorinating boreholes, and advising residents to boil water. Commonly missing data elements included specific case definitions used, testing strategy and methods, seroprevalence, impacts of interventions, and outbreak response costs. Approximately 20% of HEV outbreaks we found were not published in the peer-reviewed literature.ConclusionHEV represents a significant public health problem. Unfortunately, extensive data shortages and a lack of standardized reporting make it difficult to estimate the HEV disease burden accurately and to implement effective prevention and response activities. Our study has identified major gaps to guide future studies and outbreak reporting systems. Our results support the development of standardized reporting procedures/platforms for HEV outbreaks to ensure accurate and timely data distribution, including active and passive coordinated surveillance systems, particularly among high-risk populations.

Sexually transmitted outbreaks and genomic surveillance

Sexually transmitted outbreaks and genomic surveillance

Characterisation of Treponema pallidum lineages within the contemporary syphilis outbreak in Australia: a genomic epidemiological analysis

The incidence of syphilis has increased markedly in the past decade in high-income countries, including Australia. To date, however, genomic studies of Treponema pallidum have focused mainly on the northern hemisphere. Here, we aimed to characterise the lineages of T pallidum driving the current syphilis epidemic in Australia. In this genomic epidemiological analysis, using phylogenomic and phylodynamic analyses, we analysed 456 high-quality T pallidum genomes collected from clinical samples in Australia between Oct 19, 2005, and Dec 31, 2020, and contextualised this information with publicly available sequence data. We also performed detailed genomic characterisation of putative antimicrobial resistance determinants, in addition to correlating single-locus typing of the TP0548 allele with the T pallidum phylogeny. Phylogenomic analyses identified four major sublineages circulating in Australia and globally, two belonging to the SS14 lineage, and two belonging to the Nichols lineage. Australian sublineages were further delineated into twelve subgroups, with five of the six largest subgroups associated with men who have sex with men, and the sixth lineage was predominantly associated with heterosexual people. Most Australian T pallidum genomes (398 [87%] of 456) were genotypically macrolide resistant, and TP0548 typing correlated significantly with T pallidum genomic subgroups. These findings show that the current syphilis epidemic in Australia is driven by multiple lineages of T pallidum, rather than one distinct outbreak. Major subgroups of T pallidum in Australia have emerged within the past 30 years, are closely related to global lineages, and circulate across different sexual networks. In conjunction with improved testing and treatment, these data could better inform the control of syphilis in Australia. National Health and Medical Research Council, Australian Research Council.

A review of solar chimney for natural ventilation of residential and non-residential buildings

The requirement for passive cooling strategies in buildings has great attention in almost all countries, where hot temperatures are predominant throughout the year. The ventilation process is a crucial necessity for a healthy lifestyle and its significance is additionally highlighted through the contemporary universal outbreak of Covid-19. One of the promising applications for cooling residential buildings is the solar chimney (SC) that is particularly convenient for hot and humid climates. The solar chimney is a natural draught passive method that utilizes available solar energy to build up the stack pressure. The solar chimney participates in elevating the cooling and heating efficiency of residential/non-residential spaces. The present article introduces an overview of the operation and performance of the SC. Studying the potential design and operating parameters influencing the SC performance for natural ventilation (NV) compared to the electrical high-energy technologies to sustain the acceptable indoor climatic conditions is important. As well, the natural ventilation for harsh climate conditions using SC only is not applicable so the enhanced solar ventilation systems are studied. Combined enhanced cooling/heating energy systems based on the solar chimney are considered as an effective strategy towards low-energy consuming buildings.

The Region in Review: International Issues and Events, 2020

The Region in Review:International Issues and Events, 2020 Nic Maclellan (bio) The global Coronavirus Disease 2019 (covid-19) pandemic dominated regional and international politics throughout 2020. Despite many Pacific countries avoiding the worst impacts, the pandemic highlighted social, political, and economic inequalities, with many vulnerable communities affected by overburdened health systems, changes in food production, and disruption of the formal and informal economy. In the Pacific, there were significant economic impacts from closed borders, reduced international aviation, disrupted supply lines, and a collapse of cheap tourism (Tevi 2020). However, by closing borders, drawing on international support, and mobilizing local culture and capacity, some Island states reported no confirmed cases of covid-19 by year's end, and most avoided the catastrophe seen in Europe, the United States, and many larger developing nations. As Pacific governments turned inward to protect their own citizens, there were stresses and strains in the organizations that make up the Council of Regional Organizations of the Pacific (crop). International and regional bodies postponed face-to-face leaders' meetings, including crucial gatherings such as the annual Pacific Islands Forum (pif) and the twenty-sixth Conference of the Parties (cop26) under the United Nations (UN) Framework Convention on Climate Change, scheduled for Glasgow, Scotland, in November 2020. Throughout the year, leaders highlighted the triple challenge of health, economy, and environment: the impact on medical systems and the hazard of the SARS-CoV-2 coronavirus combined with comorbidities such as obesity and diabetes; the loss of revenues and taxation for government, with significant stimulus packages adding to national debt levels; changes in remittance flows, employment, and labor mobility in national and regional labor markets; and, above all, the ongoing climate emergency, symbolized by Tropical Cyclones Harold and Yasa. During this complex year, the challenges facing Island governments and communities were overlaid by heightened geopolitical tensions. It was a year of increased US-China jousting, combined with a crisis of democracy in the United States during and after the presidential election that saw the victory of Democrat candidate Joe Biden over incumbent President Donald Trump. Throughout 2020, the Trump administration sought to rally allies like Australia, New Zealand, Japan, France, and India in an effort to contain China's influence in the Islands region. However, most independent Forum Island Countries sought to maintain a foreign policy of "friends to all, enemies to none" and were reluctant to choose sides in this sharpening geopolitical crisis. The pandemic highlighted the interconnections of humanity across the globe. On 6 March, a cruise ship [End Page 500] passenger returning to Hawai'i was diagnosed with the SARS-CoV-2 novel coronavirus. The same day, French Polynesia's representative to the French National Assembly, Maina Sage, returned to Tahiti from Paris infected with the virus after meeting the French education minister, who was later diagnosed with covid-19. Within days, Sage was quarantined in her home. The first coronavirus-related death in the Pacific was announced in Guåhan (Guam) on 22 March, after a patient in the US territory was diagnosed with covid-19 on 15 March. With memories of the post–World War I influenza pandemic and more contemporary outbreaks of infectious disease, Pacific governments quickly closed international borders to overseas travelers in February and March 2020. By April, states and territories reported small numbers of returning nationals and overseas staff in quarantine, avoiding the widespread community transmission evident in many larger nations. Due to prompt action to ban cruise ships, strengthen quarantine systems, and boost border controls, many smaller countries, including the Cook Islands, Kiribati, Nauru, Niue, Palau, Tokelau, Tonga, and Tuvalu, reported no cases of infection throughout the year. By year's end, Vanuatu and the Federated States of Micronesia had just one case each, and Sāmoa two. In contrast, a much greater number of confirmed cases of covid-19 occurred in French Polynesia, Guåhan, Hawai'i, West Papua, Rapa Nui, the Northern Mariana Islands, and Kanaky New Caledonia, all of them colonial dependencies that do not fully control their borders. French Polynesia had just four cases in April, May, and June, but when France reopened its borders on 15 July, a surge of tourists and returning...

Right-wing populism and the criminalization of sea-rescue NGOs: the ‘Sea-Watch 3’ case in Italy, and Matteo Salvini’s communication on Facebook

The contemporary outbreak of right-wing populism in combination with increasing migratory flows toward Europe raises concerns about the social construction of migrations and migrants and the policy orientations toward them. Research indicated worrying tendencies to perceive migrations negatively and criminalize migrants. However, this paper focuses on a different tactic adopted by a number of populist forces: the criminalization of sea-rescue NGOs. In particular, it presents the case-study of Sea-Watch 3, an NGO sea-rescue vessel which docked in Italy with several migrants on board in June 2019, after a long struggle with Minister of Internal Affairs Matteo Salvini, the leader of the League (a right-wing, anti-migrants populist party). By means of content analysis, the paper discusses Salvini’s Facebook communication strategy about the event. The aim of this study is to cast new light on how the criminalization of NGOs can be exploited to reinforce other aspects of right-wing populism, such as anti-elitism, nationalism, exclusionary politics, personalization, and polarization. In this respect, the implications of criminalizing sea-rescue NGOs for policy orientations and policymaking are also highlighted.

Epidemic Alphaviruses: Ecology, Emergence and Outbreaks.

Over the past century, the emergence/reemergence of arthropod-borne zoonotic agents has been a growing public health concern. In particular, agents from the genus Alphavirus pose a significant risk to both animal and human health. Human alphaviral disease presents with either arthritogenic or encephalitic manifestations and is associated with significant morbidity and/or mortality. Unfortunately, there are presently no vaccines or antiviral measures approved for human use. The present review examines the ecology, epidemiology, disease, past outbreaks, and potential to cause contemporary outbreaks for several alphavirus pathogens.

Could Putting the Mesenchymal Stem Cells Technology into Practice Be an Optimistic Therapy for The Critically Ill COVID-19?

COVID-19 comes to light, quickly developing status. Daily, we know more about the human new coronavirus (HCoV19), which is extremely infective with heavy pneumonia connected with fast virus reproduction. Emerging in Wuhan China 31 December 2019, the contemporary COVID-19 outbreak has quickly overripe taking place directly between individuals so contagion extending to be a world health emergency at present on pandemic level. The pandemic has had deep impacts on everyday lifetime towards numerous of the world. Presently no therapy, no specified remedies or inoculations are ready to treat the patients with COVID-19 pollution and investigators here and there the globe are jostling to recognize present medication or synthesis that could be functional versus it. Therefore, there is a great unmet requirement for a secure and efficient therapy for COVID-19 contaminated cases, particularly the serious cases. What types of therapies might now assist? What are the lab craft strategies to restraining coronavirus? Ago mid-February, one tactic that has acquired rising attraction is stem cell therapy, curing that have often been saw as a potential magic bullet by despairing patients suffering from degenerative incurable conditions. In plentiful of these diseases, truth has so far to coincide with the hype. The cell based-therapy doings by supporting the body’s precocious refractory reply in an orientation that could goal the coronavirus. Now stem cell-based therapy for COVID-19 is earning incentive in China. The tally of the world emergency has visible governments frequently proclamation the company global to develop in the search for a cure, and the Australian corporate Mesoblast – a global commander in cell-based therapies for a lot of illnesses – are earned recently the approval to start clinical trials of their possess stem cell based product against COVID-19. Taking into consideration that generality of the dead sick people were produced by serious inflammation reaction, it is extremely demanding to advance efficient curative factors and strategies for that cases. I present an accurate lab modality in preparing mesenchymal stem cells (MSCs) which might be a perfect option to cure the seriously sick novel COVID-19 cases. Beneath this situation, I suppose that blood derived MSCs generated from the critically ill novel COVID-19 patient itself (autologous) suggested as a treatment for him. Therefore, my viewpoint spots a modern curative strategy.

Genomics of Serratia marcescens Isolates Causing Outbreaks in the Same Pediatric Unit 47 Years Apart: Position in an Updated Phylogeny of the Species.

The first documented nosocomial outbreak caused by Serratia marcescens in Spain occurred in 1969 at the neonatal intensive care unit (NICU) of the tertiary La Paz Children’s Hospital in Madrid, Spain, and based on the available phenotyping techniques at this time, it was considered as a monoclonal outbreak. Only 47 years later, another S. marcescens outbreak of an equivalent dimension occurred at the same NICU. The aim of the present study was to study isolates from these historical and contemporary outbreaks by phenotypic analysis and whole-genome sequencing techniques and to position these strains along with 444 publicly available S. marcescens genomes, separately comparing core genome and accessory genome contents. Clades inferred by both approaches showed high correlation, indicating that core and accessory genomes seem to evolve in the same manner for S. marcescens. Nine S. marcescens clusters were identified, and isolates were grouped in two of them according to sampling year. One exception was isolate 13F-69, the most genetically distant strain, located in a different cluster. Categorical functions in the annotated accessory genes of both collections were preserved among all isolates. No significant differences in frequency of insertion sequences in historical (0.18–0.20)—excluding the outlier strain—versus contemporary isolates (0.11–0.19) were found despite the expected resting effect. The most dissimilar isolate, 13F-69, contains a highly preserved plasmid previously described in Bordetella bronchiseptica. This strain exhibited a few antibiotic resistance genes not resulting in a resistant phenotype, suggesting the value of gene down expression in adaptation to long-term starvation.

Swarming motility and biofilm formation of Paenibacillus larvae, the etiological agent of American Foulbrood of honey bees (Apis mellifera)

American Foulbrood is a worldwide distributed, fatal disease of the brood of the Western honey bee (Apis mellifera). The causative agent of this fatal brood disease is the Gram-positive, spore-forming bacterium Paenibacillus larvae, which can be classified into four different genotypes (ERIC I-IV), with ERIC I and II being the ones isolated from contemporary AFB outbreaks. P. larvae is a peritrichously flagellated bacterium and, hence, we hypothesized that P. larvae is capable of coordinated and cooperative multicellular behaviors like swarming motility and biofilm formation. In order to analyze these behaviors of P. larvae, we firstly established appropriate functional assays. Using these assays we demonstrated that P. larvae ERIC II, but not P. larvae ERIC I, was capable of swarming. Swarming motility was hampered in a P. larvae ERIC II-mutant lacking production of paenilarvin, an iturin-like lipopeptide exclusively expressed by this genotype. Both genotypes were able to form free floating biofilm aggregates loosely attached to the walls of the culture wells. Visualizing the biofilms by Congo red and thioflavin S staining suggested structural differences between the biofilms formed. Biofilm formation was shown to be independent from paenilarvin production because the paenilarvin deficient mutant was comparably able to form a biofilm.

Abundance and Multilocus Sequence Analysis of Vibrio Bacteria Associated with Diseased Elkhorn Coral (Acropora palmata) of the Florida Keys.

The critically endangered elkhorn coral (Acropora palmata) is affected by white pox disease (WPX) throughout the Florida Reef Tract and wider Caribbean. The bacterium Serratia marcescens was previously identified as one etiologic agent of WPX but is no longer consistently detected in contemporary outbreaks. It is now believed that multiple etiologic agents cause WPX; however, to date, no other potential pathogens have been thoroughly investigated. This study examined the association of Vibrio bacteria with WPX occurrence from August 2012 to 2014 at Looe Key Reef in the Florida Keys, USA. The concentration of cultivable Vibrio was consistently greater in WPX samples than in healthy samples. The abundance of Vibrio bacteria relative to total bacteria was four times higher in samples from WPX lesions than in adjacent apparently healthy regions of diseased corals based on quantitative PCR (qPCR). Multilocus sequence analysis (MLSA) was used to assess the diversity of 69 Vibrio isolates collected from diseased and apparently healthy A. palmata colonies and the surrounding seawater. Vibrio species with known pathogenicity to corals were detected in both apparently healthy and diseased samples. While the causative agent(s) of contemporary WPX outbreaks remains elusive, our results suggest that Vibrio spp. may be part of a nonspecific heterotrophic bacterial bloom rather than acting as primary pathogens. This study highlights the need for highly resolved temporal sampling in situ to further elucidate the role of Vibrio during WPX onset and progression.IMPORTANCE Coral diseases are increasing worldwide and are now considered a major contributor to coral reef decline. In particular, the Caribbean has been noted as a coral disease hot spot, owing to the dramatic loss of framework-building acroporid corals due to tissue loss diseases. The pathogenesis of contemporary white pox disease (WPX) outbreaks in Acropora palmata remains poorly understood. This study investigates the association of Vibrio bacteria with WPX.

Computer Science and Systems Biology: Integration towards Improvement

Computer Science and Systems Biology have heralded remarkable technological advances in understanding the complex biological systems including human biochemical, molecular and neural pathways and networks. Systems biology integrates the computer applications and experimental biology in modeling’s, predictions and characterizations of complex and dynamic properties of biological systems. Particularly, multi-omics studies, high-throughput sequencing techniques and microarray techniques made possible the generation of large datasets from biological systems that could help in understanding the comprehensive molecular pathways, systems functions and behaviors. In the last decade, the computer science and systems biology approaches increased the interest in pathway based biomarker identification, identifying disease genes and drug targets, generation of global genetic interaction maps, and development of new diagnosis and therapeutics methods for deadly diseases and contemporary outbreaks. In this letter, I summarize the breakthroughs of the decade and future challenges in uncover the complex components of biological systems.

Experimental Zika Virus Inoculation in a New World Monkey Model Reproduces Key Features of the Human Infection

A monkey model of Zika virus (ZIKV) infection is urgently needed to better understand transmission and pathogenesis, given its proven association with fetal brain defects in pregnant women and acute neurological illness. Here we experimentally infected 4 male marmosets with ZIKV (prototype 1947 African strain) and monitored them clinically with sampling of various body fluids and tissues for nearly 3 months. We show that the course of acute infection with ZIKV in these New World monkeys resembles the human illness in many respects, including (1) lack of apparent clinical symptoms in most cases, (2) persistence of the virus in body fluids such as semen and saliva for longer periods of time than in serum, and (3) generation of neutralizing antibodies as well as an antiviral immunological host response. Importantly, ZIKV-infected saliva samples (in addition to serum) were found to be infectious, suggesting potential capacity for viral transmission by the oral route. Re-challenge of a previously infected marmoset with a contemporary outbreak strain SPH2015 from Brazil resulted in continued protection against infection, no viral shedding, and boosting of the immune response. Given the key similarities to human infection, a marmoset model of ZIKV infection may be useful for testing of new drugs and vaccines.

Cholera Epidemics of the Past Offer New Insights Into an Old Enemy.

Although cholera is considered the quintessential long-cycle waterborne disease, studies have emphasized the existence of short-cycle (food, household) transmission. We investigated singular Danish cholera epidemics (in 1853) to elucidate epidemiological parameters and modes of spread. Using time series data from cities with different water systems, we estimated the intrinsic transmissibility (R0). Accessing cause-specific mortality data, we studied clinical severity and age-specific impact. From physicians' narratives we established transmission chains and estimated serial intervals. Epidemics were seeded by travelers from cholera-affected cities; initial transmission chains involving household members and caretakers ensued. Cholera killed 3.4%-8.9% of the populations, with highest mortality among seniors (16%) and lowest in children (2.7%). Transmissibility (R0) was 1.7-2.6 and the serial interval was estimated at 3.7 days (95% confidence interval, 2.9-4.7 days). The case fatality ratio (CFR) was high (54%-68%); using R0 we computed an adjusted CFR of 4%-5%. Short-cycle transmission was likely critical to early secondary transmission in historic Danish towns. The outbreaks resembled the contemporary Haiti outbreak with respect to transmissibility, age patterns, and CFR, suggesting a role for broader hygiene/sanitation interventions to control contemporary outbreaks.

A Reverse Genetics Platform That Spans the Zika Virus Family Tree.

ABSTRACTZika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics.