Pandemics In History Research Articles

HIV/AIDS and Respectful Maternity Care (RMC)

With an estimate of 36.7 million people living with HIV at the end of 2016 and 1.8 million people becoming newly infected in 2016 globally, HIV continues to be a major global public health issue. Despite the virus only being identified in 1984, more than 35 million people have died of HIV or AIDS, making it one of the most destructive pandemics in history. Today, scientific advances have been made in HIV treatment, there are laws to protect people living with HIV and we know so much more about the condition. Despite this, there are several facts which are not known and the stigma and discrimination remain a reality for many people living with the condition.

“They Buckled on the Armor of God”: Kentucky Catholic Sister “Nurses” in the 1918 Flu Pandemic

During 1918, the “Spanish Flu” took millions of lives worldwide and remains the worst influenza pandemic in history. The worldwide transmission and the number of deaths from this flu were increased due to the conditions of World War I. In September 1918, the first cases of flu in Kentucky appeared at Camp Zachary Taylor, Louisville. At the time, over forty thousand troops were stationed at the camp. Within a week of the first cases being diagnosed, thousands of soldiers were ill, and the base hospital was quickly overwhelmed. By the end of September, 20 percent of the barracks had been converted to emergency hospitals, and urgent appeals went out for additional nurses. During many previous health crises within Kentucky, dating back to the early 1800s, Catholic sisters had volunteered to work as caregivers. A Roman Catholic Army chaplain at the base requested help from various orders of Kentucky nuns, and within days, eighty-eight sisters from seven orders arrived to help, despite knowing they were placing themselves at great personal risk. The majority of the sisters were teachers rather than professional nurses. The care and vigilant observation provided by the sisters was vital to saving many soldiers’ lives, yet they received little recognition for their contribution. In this year of the centenary of the flu pandemic and the end of the war, it is appropriate to acknowledge the work of the sisters who sacrificed to help the stricken soldiers.

Seasonality in risk of pandemic influenza emergence

Influenza pandemics can emerge unexpectedly and wreak global devastation. However, each of the six pandemics since 1889 emerged in the Northern Hemisphere just after the flu season, suggesting that pandemic timing may be predictable. Using a stochastic model fit to seasonal flu surveillance data from the United States, we find that seasonal flu leaves a transient wake of heterosubtypic immunity that impedes the emergence of novel flu viruses. This refractory period provides a simple explanation for not only the spring-summer timing of historical pandemics, but also early increases in pandemic severity and multiple waves of transmission. Thus, pandemic risk may be seasonal and predictable, with the accuracy of pre-pandemic and real-time risk assessments hinging on reliable seasonal influenza surveillance and precise estimates of the breadth and duration of heterosubtypic immunity.

West Africa’s Ebola Pandemic: Toward Effective Multilateral Responses to Health Crises

The Ebola virus disease (EVD) outbreak in West Africa in 2014 became the region's most dangerous pandemic in history. Initially misdiagnosed by health authorities in Liberia, Guinea, and Sierra Leone, the epicenters of the crises, the wider health infrastructure of the international community similarly failed to grasp the enormity of the challenge posed by this pandemic to West Africa and its potential global ramifications. By the time recognition dawned about the immensity of the challenges that were posed by this pandemic, it took the introduction of extraordinary measures through the characterization of the disease as a threat to international peace and security pursuant to Chapter VII of the UN Charter to get the necessary institutional and bureaucratic machineries to intervene. This article argues that EVD, disastrous in its outcome, exposed the weaknesses and failures of existing institutional frameworks at national, regional, and continental to global levels. Focusing primarily on multilateral responses (the UN, the African Union [AU], and the Economic Community of West African States [ECOWAS]) to the epidemic, this article argues for enhanced global-regional collaboration in the context of the UN Charter's Chapter VIII for more effective future responses to health crises in West Africa. This article contributes to the ongoing debate on the reform of global health governance by analyzing the existing health governance strategies established by ECOWAS and implemented through the West African Health Organization.

The Molecular Mechanisms Underlying the Hijack of Host Proteins by the 1918 Spanish Influenza Virus.

The 1918 Spanish influenza A virus (IAV) caused one of the most serious pandemics in history. The nonstructural protein 1 (NS1) of the 1918 IAV hijacks the interaction between human CrkII and JNK1. Little is, however, known about its molecular mechanism. Here, we performed X-ray crystallography, NMR relaxation dispersion experiment, and fluorescence spectroscopy to determine the structural, kinetic, and thermodynamic mechanisms underlying the hijacking of CrkII by 1918 IAV NS1. We observed that the interaction between a proline-rich motif in NS1 and the N-terminal SH3 domain of CrkII displays strikingly rapid kinetics and exceptionally high affinity with 100-fold faster kon and 3300-fold lower Kd compared to those for the CrkII-JNK1 interaction. These results provide molecular insight into the mechanism by which 1918 IAV NS1 hijacks CrkII and disrupts its interactions with critical cellular signaling proteins.

The ghost of pandemics past: revisiting two centuries of influenza in Sweden

Previous influenza pandemics are usually invoked in pandemic preparedness planning without a thorough analysis of the events surrounding them, what has been called the ‘configuration’ of epidemics. Historic pandemics are...

Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of Historical Data from Switzerland.

BackgroundTuberculosis (TB) mortality declined in the northern hemisphere over the last 200 years, but peaked during the Russian (1889) and the Spanish (1918) influenza pandemics. We studied the impact of these two pandemics on TB mortality.MethodsWe retrieved historic data from mortality registers for the city of Bern and countrywide for Switzerland. We used Poisson regression models to quantify the excess pulmonary TB (PTB) mortality attributable to influenza.ResultsYearly PTB mortality rates increased during both influenza pandemics. Monthly influenza and PTB mortality rates peaked during winter and early spring. In Bern, for an increase of 100 influenza deaths (per 100,000 population) monthly PTB mortality rates increased by a factor of 1.5 (95%Cl 1.4–1.6, p<0.001) during the Russian, and 3.6 (95%Cl 0.7–18.0, p = 0.13) during the Spanish pandemic. Nationally, the factor was 2.0 (95%Cl 1.8–2.2, p<0.001) and 1.5 (95%Cl 1.1–1.9, p = 0.004), respectively. We did not observe any excess cancer or extrapulmonary TB mortality (as a negative control) during the influenza pandemics.ConclusionsWe demonstrate excess PTB mortality during historic influenza pandemics in Switzerland, which supports a role for influenza vaccination in PTB patients in high TB incidence countries.

Mortality and transmissibility patterns of the 1957 influenza pandemic in Maricopa County, Arizona.

BackgroundWhile prior studies have quantified the mortality burden of the 1957 H2N2 influenza pandemic at broad geographic regions in the United States, little is known about the pandemic impact at a local level. Here we focus on analyzing the transmissibility and mortality burden of this pandemic in Arizona, a setting where the dry climate was promoted as reducing respiratory illness transmission yet tuberculosis prevalence was high.MethodsUsing archival death certificates from 1954 to 1961, we quantified the age-specific seasonal patterns, excess-mortality rates, and transmissibility patterns of the 1957 H2N2 pandemic in Maricopa County, Arizona. By applying cyclical Serfling linear regression models to weekly mortality rates, the excess-mortality rates due to respiratory and all-causes were estimated for each age group during the pandemic period. The reproduction number was quantified from weekly data using a simple growth rate method and assumed generation intervals of 3 and 4 days. Local newspaper articles published during 1957–1958 were also examined.ResultsExcess-mortality rates varied between waves, age groups, and causes of death, but overall remained low. From October 1959-June 1960, the most severe wave of the pandemic, the absolute excess-mortality rate based on respiratory deaths per 10,000 population was 16.59 in the elderly (≥65 years). All other age groups exhibit very low excess-mortality and the typical U-shaped age-pattern was absent. However, the standardized mortality ratio was greatest (4.06) among children and young adolescents (5–14 years) from October 1957-March 1958, based on mortality rates of respiratory deaths. Transmissibility was greatest during the same 1957–1958 period, when the mean reproduction number was estimated at 1.08–1.11, assuming 3- or 4-day generation intervals with exponential or fixed distributions.ConclusionsMaricopa County exhibited very low mortality impact associated with the 1957 influenza pandemic. Understanding the relatively low excess-mortality rates and transmissibility in Maricopa County during this historic pandemic may help public health officials prepare for and mitigate future outbreaks of influenza.

The effect of growth temperature on the nanoscale biochemical surface properties of Yersinia pestis.

Yersinia pestis, the causative agent of plague, has been responsible for several recurrent, lethal pandemics in history. Currently, it is an important pathogen to study owing to its virulence, adaptation to different environments during transmission, and potential use in bioterrorism. Here, we report on the changes to Y. pestis surfaces in different external microenvironments, specifically culture temperatures (6, 25, and 37°C). Using nanoscale imaging coupled with functional mapping, we illustrate that changes in the surfaces of the bacterium from a morphological and biochemical standpoint can be analyzed simultaneously using atomic force microscopy. The results from functional mapping, obtained at a single cell level, show that the density of lipopolysaccharide (measured via terminal N-acetylglucosamine) on Y. pestis grown at 37°C is only slightly higher than cells grown at 25°C, but nearly three times higher than cells maintained at 6°C for an extended period of time, thereby demonstrating that adaptations to different environments can be effectively captured using this technique. This nanoscale evaluation provides a new microscopic approach to study nanoscale properties of bacterial pathogens and investigate adaptations to different external environments.

Historical Y.pestis Genomes Reveal the European Black Death as the Source of Ancient and Modern Plague Pandemics.

Ancient DNA analysis has revealed an involvement ofthe bacterial pathogen Yersinia pestis in several historical pandemics, including the second plague pandemic (Europe, mid-14(th) century Black Death until the mid-18(th) century AD). Here we present reconstructed Y.pestis genomes from plague victims of the Black Death and two subsequent historical outbreaks spanning Europe and its vicinity, namely Barcelona, Spain (1300-1420 cal AD), Bolgar City, Russia (1362-1400 AD), and Ellwangen, Germany (1485-1627 cal AD). Our results provide support for (1) a single entry of Y.pestis in Europe during the Black Death, (2) a wave of plague that traveled toward Asia to later become the source population for contemporary worldwide epidemics, and (3) the presence of an historical European plague focus involved in post-Black Death outbreaks that is now likely extinct.

Mortality risk factors show similar trends in modern and historic populations exposed to plague

Plague has been responsible for two major historic pandemics (6th-8th century CE; 14th-19th century CE) and a modern one. The recent Malagasy plague outbreaks raised new concerns on the deadly potential of the plague-causing bacteria Yersinia pestis. Between September 2014 and April 2015, outbreaks of bubonic and pneumonic plague hit the Malagasy population. Two hundred and sixty-three cases, including 71 deaths, have been reported in 16 different districts with a case fatality rate of 27%. The scope of our study was to ascertain whether the risk factors for health in modern-day populations exposed to plague and in ancient populations that faced the two historic pandemics varied or remained substantially unaltered. The risk of mortality of the Malagasy population with those obtained from the reconstruction of three samples of European populations exposed to the historic pandemics was contrasted. The evidence shows that the risks of death are not uniform across age neither in modern nor in historic populations exposed to plague and shows precise concentrations in specific age groups (children between five and nine years of age and young adults). Although in the post-antibiotic era, the fatality rates have drastically reduced, both modern and historic populations were exposed to the same risk factors that are essentially represented by a low standard of environmental hygiene, poor nutrition, and weak health systems.

Immunology of Yersinia pestis Infection.

As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

Discovery of the Plague Pathogen: Lessons Learned.

Plague resulted in three pandemics in history; however, its causative pathogen was isolated until the third pandemic in Hong Kong in 1894. At that time, two famous researchers, Dr. Alexandre Yersin and Dr. Shibasaburo Kitasato, went to HK, in order to identify the pathogen. The two great researchers had done a lot of work to isolate and identify the causative pathogen. However, Dr. Alexandre Yersin reported the real pathogen for plague, and we now acknowledge his work by nominating the pathogen's genus as Yersinia. In this chapter, we discussed the lessons learned from the two researchers' experience on isolation and identification of plague pathogen.

Genome and Evolution of Yersinia pestis.

This chapter summarizes researches on genome and evolution features of Yersinia pestis, the young pathogen that evolved from Y. pseudotuberculosis at least 5000 years ago. Y. pestis is a highly clonal bacterial species with closed pan-genome. Comparative genomic analysis revealed that genome of Y. pestis experienced highly frequent rearrangement and genome decay events during the evolution. The genealogy of Y. pestis includes five major branches, and four of them seemed raised from a "big bang" node that is associated with the Black Death. Although whole genome-wide variation of Y. pestis reflected a neutral evolutionary process, the branch length in the genealogical tree revealed over dispersion, which was supposedly caused by varied historical molecular clock that is associated with demographical effect by alternate cycles of enzootic disease and epizootic disease in sylvatic plague foci. In recent years, palaeomicrobiology researches on victims of the Black Death, and Justinian's plague verified that two historical pandemics were indeed caused by Y. pestis, but the etiological lineages might be extinct today.

The challenge of resistance in antimicrobial drug development.

Man has long battled the infectious diseases caused by pathogenic bacteria, fungi, protozoa and viruses. Since the late 1930s, the discovery and development of chemotherapeutic agents has been the central effort toward combating infectious disease. Although many of the major causes of historical pandemics no longer present the threat they once did and we have experienced a multidecade era in which safe and effective antibiotics were plentiful, we are now witnessing the emergence of organisms resistant to the most efficacious agents. The adaptive nature of the pathogens necessitates the discovery of new effective compounds or the re-engineering of existing molecules to combat the resistant organisms. This iterative cycle of discovery and development is a unique hallmark of drug discovery targeting proliferating cells. All major classes of agents with antibacterial, antifungal, antiprotozoal and antiviral activity are subject to lost efficacy owing to resistance through a multitude of pathways. Common mechanisms of resistance and examples of affected classes include point mutations in the target (HIV reverse transcriptase inhibitors), upregulation of efflux pumps (fluoroquinolones), gene amplification or development of bypass pathways (fluconazole) and drug alteration ( β-lactamase activity targeting cephalosporins). As each of these mechanisms is unique to the particular drug:organism system, carefully tailored solutions are necessary to overcome the resistance. Modern medicinal chemistry has confronted numerous resistant organisms with a variety of approaches including the discovery of novel agents without cross-resistance, use of combination therapy, or most frequently, alteration of the chemical structure to circumvent the resistance mechanism. For example, the discovery and development of daptomycin to treat methicillin-resistant Staphylococcus aureus relied on a natural product with a novel mechanism of action. The development of highly active antiretroviral therapy (HAART), a combination of multiple antiviral agents, revolutionized the treatment of HIV. Finally, no class better exemplifies the value of refinement through medicinal chemistry than the β-lactam antibiotics; many successive generations in this class have overcome β-lactamase activity while increasing the spectrum of coverage. In this issue, notable advances in understanding and overcoming resistance in a variety of disease states are presented, including a modern overview of natural product sources for discovery [1], application of combination therapy to prevent resistance [2] and a description of a structure-based approach to antibiotic redesign to evade resistant drug targets [3]. This is followed by more specific approaches to antibiotic resistance in tuberculosis [4], as well as discussion of the critical issue of “The adaptive nature of the pathogens necessitates the discovery of new effective compounds or the re-engineering of existing molecules to combat the resistant organisms.”

Redefining the differences in gene content between Yersinia pestis and Yersinia pseudotuberculosis using large-scale comparative genomics.

Yersinia pestis, the causative agent of plague, is best known for historical pandemics, but still actively causes disease in many parts of the world. Y. pestis is a recently derived clone of the pathogenic species Yersinia pseudotuberculosis, but is more associated with human infection. Numerous studies have documented genomic changes since the two species differentiated, although all of these studies used a relatively small sample set for defining these differences. In this study, we compared the complete genomic content between a diverse set of Y. pestis and Y. pseudotuberculosis genomes, and identified unique loci that could serve as diagnostic markers or for better understanding the evolution and pathogenesis of each group. Comparative genomics analyses also identified subtle variations in gene content between individual monophyletic clades within these species, based on a core genome single nucleotide polymorphism phylogeny that would have been undetected in a less comprehensive genome dataset. We also screened loci that were identified in other published studies as unique to either species and generally found a non-uniform distribution, suggesting that the assignment of these unique genes to either species should be re-evaluated in the context of current sequencing efforts. Overall, this study provides a high-resolution view into the genomic differences between Y. pestis and Y. pseudotuberculosis, demonstrating fine-scale differentiation and unique gene composition in both species.

The trophic responses of two different rodent-vector-plague systems to climate change.

Plague, the causative agent of three devastating pandemics in history, is currently a re-emerging disease, probably due to climate change and other anthropogenic changes. Without understanding the response of plague systems to anthropogenic or climate changes in their trophic web, it is unfeasible to effectively predict years with high risks of plague outbreak, hampering our ability for effective prevention and control of the disease. Here, by using surveillance data, we apply structural equation modelling to reveal the drivers of plague prevalence in two very different rodent systems: those of the solitary Daurian ground squirrel and the social Mongolian gerbil. We show that plague prevalence in the Daurian ground squirrel is not detectably related to its trophic web, and that therefore surveillance efforts should focus on detecting plague directly in this ecosystem. On the other hand, plague in the Mongolian gerbil is strongly embedded in a complex, yet understandable trophic web of climate, vegetation, and rodent and flea densities, making the ecosystem suitable for more sophisticated low-cost surveillance practices, such as remote sensing. As for the trophic webs of the two rodent species, we find that increased vegetation is positively associated with higher temperatures and precipitation for both ecosystems. We furthermore find a positive association between vegetation and ground squirrel density, yet a negative association between vegetation and gerbil density. Our study thus shows how past surveillance records can be used to design and improve existing plague prevention and control measures, by tailoring them to individual plague foci. Such measures are indeed highly needed under present conditions with prevailing climate change.

Pandemics and Urban Child Survival: Pulling Together in the Adoption Canoe

This article tells an intergenerational narrative about how historical pandemics and family adoptions stories can influence urban Indigenous custom adoption practices, policies, teaching and research. It uses the seven principles of Archibald’s (2008) storywork to link the importance of knowing our own family histories, and how those historical, cultural and current contexts can be a force to advocate, influence, research and teach for change. The “canoe” is a metaphor for re-conceptualizing adoption narratives, and emphasizes the idea of an “adoption journey” or a shared learning process.

Fractal cycle turning points: A theory of human social progression

Throughout history, rare, influential, unexpected, catastrophic events with widespread significant long-term effects such as societal collapse, wars, revolutions, natural disasters, disease pandemics, droughts, famines, and financial crises have impacted humanity at large. These events seem to occur infrequently in a random manner that makes their prediction difficult. I examined closely the seemingly “random” occurrence of these events and observed a peculiar pattern: they occur at Fibonacci intervals and exhibit the irregular regularity of fractal phenomena. I identify three unique sets of patterns, to which I refer as cycles: (1) the Kuwae Cycle, (2) the Tambora Cycle, and (3) the Deflationary Cycle. They closely align with significant historical events, disease pandemics, famines, revolutions and warfare in England and the United States, and link to anomalous weather patterns induced by volcanism, heat, cold, rain and drought, all of which influence harvests dating back to the 6th century. These patterns also correlate with commodity price changes for which we have good data to study their behavior. Using commodities data, I show that, not only are commodity price changes closely associated with large historical events, but that they also occur at Fibonacci intervals in a complex cyclical and fractal manner. Short-term price cycles are part of larger fractal price waves which are themselves part of higher order fractals that measure the rise and fall of civilizations. I develop an algorithm that defines the cyclical nature and importance of Fibonacci intervals and advance a “Fractal Cycle Turning Point Theory” that explains historical price patterns and makes predictions about future price cycles, disease pandemics, warfare, financial crises and other influential events.

Death patterns during the 1918 influenza pandemic in Chile.

Scarce information about the epidemiology of historical influenza pandemics in South America prevents complete understanding of pandemic patterns throughout the continent and across different climatic zones. To fill gaps with regard to spatiotemporal patterns of deaths associated with the 1918 influenza pandemic in Chile, we reviewed archival records. We found evidence that multiple pandemic waves at various times of the year and of varying intensities occurred during 1918-1921 and that influenza-related excess deaths peaked during July-August 1919. Pandemic-associated mortality rates were elevated for all age groups, including for adults >50 years of age; elevation from baseline was highest for young adults. Overall, the rate of excess deaths from the pandemic was estimated at 0.94% in Chile, similar to rates reported elsewhere in Latin America, but rates varied ≈10-fold across provinces. Patterns of death during the pandemic were affected by variation in host-specific susceptibility, population density, baseline death rate, and climate.