Showing papers on "Plague (disease) published in 2012"

Transmission of Flea-Borne Zoonotic Agents*

Abstract: Flea-borne zoonoses such as plague (Yersinia pestis) and murine typhus (Rickettsia typhi) caused significant numbers of human cases in the past and remain a public health concern. Other flea-borne human pathogens have emerged recently (e.g., Bartonella henselae, Rickettsia felis), and their mechanisms of transmission and impact on human health are not fully understood. Our review focuses on the ecology and epidemiology of the flea-borne bacterial zoonoses mentioned above with an emphasis on recent advancements in our understanding of how these organisms are transmitted by fleas, maintained in zoonotic cycles, and transmitted to humans. Emphasis is given to plague because of the considerable number of studies generated during the first decade of the twenty-first century that arose, in part, because of renewed interest in potential agents of bioterrorism, including Y. pestis.

Insights from genomic comparisons of genetically monomorphic bacterial pathogens

Abstract: Some of the most deadly bacterial diseases, including leprosy, anthrax and plague, are caused by bacterial lineages with extremely low levels of genetic diversity, the so-called ‘genetically monomorphic bacteria’. It has only become possible to analyse the population genetics of such bacteria since the recent advent of high-throughput comparative genomics. The genomes of genetically monomorphic lineages contain very few polymorphic sites, which often reflect unambiguous clonal genealogies. Some genetically monomorphic lineages have evolved in the last decades, e.g. antibiotic-resistant Staphylococcus aureus, whereas others have evolved over several millennia, e.g. the cause of plague, Yersinia pestis. Based on recent results, it is now possible to reconstruct the sources and the history of pandemic waves of plague by a combined analysis of phylogeographic signals in Y. pestis plus polymorphisms found in ancient DNA. Different from historical accounts based exclusively on human disease, Y. pestis evolved in China, or the vicinity, and has spread globally on multiple occasions. These routes of transmission can be reconstructed from the genealogy, most precisely for the most recent pandemic that was spread from Hong Kong in multiple independent waves in 1894.

Plague vaccines: current developments and future perspectives.

Abstract: Despite many decades of intensive studies of Yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease. A recently developed F1/V subunit vaccine candidate, which relies mainly on humoral immunity, showed promising results in animal studies; however, its efficacy in humans still has to be carefully evaluated. In addition, those developing next-generation plague vaccines need to pay particular attention to the importance of eliciting cell-mediated immunity. In this review, we analyzed the current progress in developing subunit, DNA and live carrier platforms of delivery by bacterial and viral vectors, as well as approaches for controlled attenuation of virulent strains of Y. pestis.

Hereditary Hemochromatosis Restores the Virulence of Plague Vaccine Strains

Abstract: Yersinia pestis is the causative agent of plague, an ancient scourge that precipitates intermittent pandemics [1, 2]. Plague is a disease of mammals that is transmitted by fleabite or aerosol droplets, causing either bubonic or pneumonic plague [3]. Inoculation of humans with live-attenuated Y. pestis strains, identified as nonpigmented (pgm) colonies on hemin agar, affords protection against bubonic and pneumonic plague [4]. Nonpigmented strains, most notably Y. pestis EV76, have been used extensively as live-attenuated vaccines to successfully stem the spread of the last plague pandemic in Asia [5]. The pathogenesis of Y. pestis infections relies on the pathogen's type III secretion pathway, which delivers Yop effectors into immune cells via type III needle complexes that are capped by the protective antigen LcrV [6–8]. The protective immunity raised by live-attenuated plague vaccines is based on antibodies that are directed against the fraction 1 capsular antigen (Caf1, or F1 pilus) of Y. pestis and that interfere with the delivery of effectors by LcrV-capped type III needle complexes [9, 10]. Y. pestis variants defective for the expression of F1 capsular antigen caused plague in animals that had been immunized with the live-attenuated vaccine, indicating that protection is not universal for all Y. pestis isolates [10]. Spontaneous excision and loss of the 102-kb high-pathogenicity island and pigmentation (pgm) locus occurs on the Y. pestis chromosome at flanking IS100 elements [11, 12]. Y. pestis pgm strains are attenuated in animal models of bubonic and pneumonic plague because of their inability to synthesize yersiniabactin, a siderophore that scavenges iron from transferrin during host infection [13, 14]. Live-attenuated pgm plague vaccine–related illnesses were not reported during the immunization campaign involving Asian populations [5]. However, in a small clinical trial in the United States, some recipients of the live-attenuated plague vaccine experienced malaise, fever, and severe reactogenicity requiring hospitalization [4]. Recently, the nonpigmented Y. pestis strain UC91309 was isolated from a researcher with fatal, septicemic plague [15]. Genome sequencing suggested that the isolated strain had been acquired in the laboratory [15]. Autopsy findings included abnormally high levels of iron deposits in the liver and markedly elevated levels of serum ferritin, iron, total iron-binding capacity, and iron saturation [15]. The presence of a HFE C282Y mutation supported the postmortem diagnosis of hereditary hemochromatosis [15]. These clinical and pathological findings suggested that iron overload in tissues of an individual with hereditary hemochromatosis may complement the iron-scavenging defect in mutants that are unable to synthesize yersiniabactin, thereby restoring the virulence of pgm variants and their ability to cause plague. Formal proof for this hypothesis is not yet available. To address this question, we analyzed the virulence properties of Y. pestis UC91309 and used a mouse model of hereditary hemochromatosis to examine whether increased iron load in host tissues may restore the virulence of nonpigmented Y. pestis strains. Further, we asked whether the rV10-2 plague subunit vaccine [16], which elicits LcrV-specific antibodies that block Y. pestis type III injection of immune cells [17], can protect mice with hereditary hemochromatosis against plague disease.

Sylvatic plague vaccine: a new tool for conservation of threatened and endangered species?

Abstract: Plague, a disease caused by Yersinia pestis introduced into North America about 100 years ago, is devastating to prairie dogs and the highly endangered black-footed ferret. Current attempts to control plague in these species have historically relied on insecticidal dusting of prairie dog burrows to kill the fleas that spread the disease. Although successful in curtailing outbreaks in most instances, this method of plague control has significant limitations. Alternative approaches to plague management are being tested, including vaccination. Currently, all black-footed ferret kits released for reintroduction are vaccinated against plague with an injectable protein vaccine, and even wild-born kits are captured and vaccinated at some locations. In addition, a novel, virally vectored, oral vaccine to prevent plague in wild prairie dogs has been developed and will soon be tested as an alternative, preemptive management tool. If demonstrated to be successful, oral vaccination of selected prairie dog populations could decrease the occurrence of plague epizootics in key locations, thereby reducing the source of bacteria while avoiding the indiscriminate environmental effects of dusting. Just as rabies in wild carnivores has largely been controlled through an active surveillance and oral vaccination program, we believe an integrated plague management strategy would be similarly enhanced with the addition of a cost-effective, bait-delivered, sylvatic plague vaccine for prairie dogs. Control of plague in prairie dogs, and potentially other rodents, would significantly advance prairie dog conservation and black-footed ferret recovery.

Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus

Abstract: Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (∼725–1160 m) to higher elevation sites within the focus (∼1380–1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence.

Identification of Chinese plague foci from long-term epidemiological data.

Abstract: Carrying out statistical analysis over an extensive dataset of human plague reports in Chinese villages from 1772 to 1964, we identified plague endemic territories in China (i.e., plague foci). Analyses rely on (i) a clustering method that groups time series based on their time-frequency resemblances and (ii) an ecological niche model that helps identify plague suitable territories characterized by value ranges for a set of predefined environmental variables. Results from both statistical tools indicate the existence of two disconnected plague territories corresponding to Northern and Southern China. Altogether, at least four well defined independent foci are identified. Their contours compare favorably with field observations. Potential and limitations of inferring plague foci and dynamics using epidemiological data is discussed.

Factors Affecting the Spread and Maintenance of Plague

Abstract: Plague is characterized by its potentially explosive spread during human epidemics and rodent epizootics. Recent research has suggested how this spread is likely to occur and what factors are associated with the onset of plague outbreaks and the continued spread of the disease. Among the apparent drivers of these outbreaks are climatic variables, host and vector densities, percolation thresholds, and the ability of many fleas to transmit efficiently soon after taking an infectious blood meal and before Yersinia pestis biofilm-related blockages appear in their guts. This presentation discusses each of these topics and their likely contribution to the rapid spread of plague to humans and in natural systems.

The model of Kermack and McKendrick for the plague epidemic in Bombay and the type reproduction number with seasonality

Abstract: The figure showing how the model of Kermack and McKendrick fits the data from the 1906 plague epidemic in Bombay is the most reproduced figure in books discussing mathematical epidemiology. In this paper we show that the assumption of constant parameters in the model leads to quite unrealistic numerical values for these parameters. Moreover the reports published at the time show that plague epidemics in Bombay occurred in fact with a remarkable seasonal pattern every year since 1897 and at least until 1911. So the 1906 epidemic is clearly not a good example of epidemic stopping because the number of susceptible humans has decreased under a threshold, as suggested by Kermack and McKendrick, but an example of epidemic driven by seasonality. We present a seasonal model for the plague in Bombay and compute the type reproduction numbers associated with rats and fleas, thereby extending to periodic models the notion introduced by Roberts and Heesterbeek.

Digitizing Historical Plague

Abstract: TO THE EDITOR– Outbreaks of bubonic plague initiated by the flea-borne bacterium Yersinia pestis have repeatedly afflicted the Old World since the onset of the ‘Justinian Plague’ in 541 AD [1]. The second European pandemic, the ‘Black Death’ rapidly killed around half of the population during 1347–1353 AD. Both pandemics then persisted with recurrent local outbreaks over several centuries. The reason for the eventual cessation of each pandemic remains mysterious [1], particularly in light of continued activity in Asia [2] where the infection is enzootic in its natural rodent hosts [3]. Socio-political influences have often compounded the complexity of plague ecology, likely increasing the spillover of infection into human populations [1–3]. The threat from the plague bacillus, which still induces several thousand human cases annually, may well increase under projected climate change [1] – and, ominously, within the context of bioterrorism [4]. Knowledge of plague ecology, epidemiology, and pathophysiology is,

A Regional Climatography of West Nile, Uganda, to Support Human Plague Modeling

Abstract: The West Nile region in northwestern Uganda is a focal point for human plague, which peaks in boreal autumn and is spread by fleas that travel on rodent hosts. The U.S. Centers for Disease Control and Prevention is collaborating with the National Center for Atmospheric Research to quantitatively address the linkages between climate and human plague in this region. The aim of this paper is to advance knowledge of the climatic conditions required to maintain enzootic cycles and to trigger epizootic cycles and ultimately to target limited surveillance, prevention, and control resources. A hybrid dynamical–statistical downscaling technique was applied to simulations from the Weather Research and Forecasting Model (WRF) to generate a multiyear 2-km climate dataset for modeling plague in the West Nile region. The resulting dataset resolves the spatial variability and annual cycle of temperature, humidity, and rainfall in West Nile relative to satellite-based and in situ records. Topography exerts a firs...

Encyclopedia of the Black Death

Abstract: This encyclopedia provides 300 interdisciplinary, cross-referenced entries that document the effect of the plague on Western society across the four centuries of the second plague pandemic, balancing medical history and technical matters with historical, cultural, social, and political factors. * 300 A-Z interdisciplinary entries on medical matters and historical issues * Each entry includes up-to-date resources for further research

Evidence of Yersinia pestis DNA from fleas in an endemic plague area of Zambia

Abstract: Background: Yersinia pestis is a bacterium that causes plague which infects a variety of mammals throughout the world. The disease is usually transmitted among wild rodents through a flea vector. The sources and routes of transmission of plague are poorly researched in Africa, yet remains a concern in several sub-Saharan countries. In Zambia, the disease has been reported on annual basis with up to 20 cases per year, without investigating animal reservoirs or vectors that may be responsible in the maintenance and propagation of the bacterium. In this study, we undertook plague surveillance by using PCR amplification of the plasminogen activator gene in fleas. Findings: Xenopsylla species of fleas were collected from 83 rodents trapped in a plague endemic area of Zambia. Of these rodents 5 had fleas positive (6.02%) for Y. pestis plasminogen activator gene. All the Y. pestis positive rodents were gerbils. Conclusions: We conclude that fleas may be responsible in the transmission of Y. pestis and that PCR may provide means of plague surveillance in the endemic areas of Zambia.

Yersinia pestis: examining wildlife plague surveillance in China and the USA

Abstract: Plague is a zoonotic disease caused by the bacterium Yersinia pestis Lehmann and Neumann, 1896. Although it is essentially a disease of rodents, plague can also be transmitted to people. Historically, plague has caused massive morbidity and mortality events in human populations, and has recently been classified as a reemerging disease in many parts of the world. This public health threat has led many countries to set up wild and domestic animal surveillance programs in an attempt to monitor plague activity that could potentially spill over into human populations. Both China and the USA have plague surveillance programs in place, but the disease dynamics differ in each country. We present data on plague seroprevalence in wildlife and review different approaches for plague surveillance in the 2 countries. The need to better comprehend plague dynamics, combined with the fact that there are still several thousand human plague cases per year, make well-designed wildlife surveillance programs a critical part of both understanding plague risks to humans and preventing disease outbreaks in the future.

The Great Manchurian Plague of 1910-1911: The Geopolitics of an Epidemic Disease

Abstract: Séquard’s discoveries further, yet to understand how they did that would require a very different book focused on the intellectual history of neurology and neuroscience. Aminoff ’s desire to make BrownSéquard relevant for his audience at times therefore skirts uncomfortably near polemic, which creates some obstacles to understanding fully the context of the controversies surrounding, for example, BrownSéquard’s infamous self-experimentation with testicular extracts in his advanced years. There is, as well, the difficulty of understanding so many social, cultural, and political landscapes as a study of BrownSéquard’s life demands, and Aminoff—as I imagine any biographer of Brown-Séquard would—struggles with the hefty challenge represented by the unwieldy long nineteenth century in France, Britain, and America. In a way, however, such nitpicking is unfair. Aminoff ’s study is rich, valuable, and original. It justifies and does justice to its subject. Brown-Séquard: An Improbable Genius Who Transformed Medicine is enjoyable and will rightly attract the interest of a wide audience of students and clinicians.

Misidentification of Yersinia pestis by Automated Systems, Resulting in Delayed Diagnoses of Human Plague Infections—Oregon and New Mexico, 2010–2011

Abstract: One human plague case was reported in Oregon in September 2010 and another in New Mexico in May 2011. Misidentification of Yersinia pestis by automated identification systems contributed to delayed diagnoses for both cases.

The plague of Thebes, a historical epidemic in Sophocles' Oedipus Rex.

Abstract: Sophocles, one of the most noted playwrights of the ancient world, wrote the tragedy Oedipus Rex in the first half of the decade 430-420 bc. A lethal plague is described in this drama. We adopted a critical approach to Oedipus Rex in analyzing the literary description of the disease, unraveling its clinical features, and defining a possible underlying cause. Our goals were to clarify whether the plague described in Oedipus Rex reflects an actual historical event; to compare it with the plague of Athens, which was described by Thucydides as occurring around the same time Sophocles wrote; and to propose a likely causative pathogen. A critical reading of Oedipus Rex and a comparison with Thucydides' history, as well as a systematic review of historical data, strongly suggests that this epidemic was an actual event, possibly caused by Brucella abortus.

Transmission dynamics of primary pneumonic plague in the USA.

Abstract: Plague is thought to have killed millions during three catastrophic pandemics. Primary pneumonic plague, the most severe form of the disease, is transmissible from person-to-person and has the potential for propagating epidemics. Efforts to quantify its transmission potential have relied on published data from large outbreaks, an approach that artificially inflates the basic reproductive number (R(0)) and skews the distribution of individual infectiousness. Using data for all primary pneumonic plague cases reported in the USA from 1900 to 2009, we determined that the majority of cases will fail to transmit, even in the absence of antimicrobial treatment or prophylaxis. Nevertheless, potential for sustained outbreaks still exists due to superspreading events. These findings challenge current concepts regarding primary pneumonic plague transmission.

Plague Hospitals: Public Health for the City in Early Modern Venice

Abstract: Contents: Introduction a "From a distance it looks like a castlea (TM): first impressions and architectural design The sick-poor a "Abandon hope, all you who enter herea (TM): experiences of staff and the patientsa (TM) daily routine Syrups and secrets: treating the plague Dying in the lazaretti Returning to the city Conclusion Epilogue Bibliography Index.

Can phage effectively treat multidrug-resistant plague?

Abstract: The spread of natural or weaponized drug-resistant plague among humans is a credible high consequence threat to public health that demands the prompt introduction of alternatives to antibiotics such as bacteriophage. Early attempts to treat plague with phages in the 1920s–1930s were sometimes promising but mostly failed, purportedly due to insufficient knowledge of phage biology and poor experimental design. We recently reported the striking stability of plague diagnostic bacteriophages, their safety for animal use, propagation in vivo and partial protection of mice from deadly plague after a single injection of phage. In this addendum we reflect on that article, other recent publications and our unpublished data, and discuss the prospects of phage therapy against plague.

The Spanish Flu - Part II: the second and third wave Španska groznica - II deo: drugi i trei talas

Abstract: The second wave of influenza pandemic of 1918 represents a period in which the Spanish Flu showed its full deadly potential It is usually said that this wave struck in autumn 1918, although the disease had spread even before this time A US naval intelligence officer received a telegram on August 3, 1918 which he immediately stamped as a secret and classified document While indicating that his source was reliable, he reported to the competent authorities: „I am confidentially advised that the disease now epidemic throughout Switzerland is what is commonly known as the black plague, although it is designated as Spanish sickness and grip“ The comparison of the Spanish Flu with plague was not a rarity already at the beginning of the second wave of the pandemic Doctors reached this conclusion, that it was a question of plague, based on the appearance of the lungs in autopsy Until then, flu did not leave this kind of a picture, thus many believed that it was a question or either a new disease or lung plague An increase in the frequency of the illstricken with flu occurred in some places with mutual distances of thousands of kilometers in August 1918, but this time with a large number of severe cases An epidemiological study, written in the States, relatively shortly after the pandemic, indicated that a progressive increase in the number of flu cases was observed in the American military bases in the week ending August 4, 1918, whereas pneumonia cases started appearing in the week ending August 18, 1918

Comparative Genomics of 2009 Seasonal Plague (Yersinia pestis) in New Mexico

Abstract: Plague disease caused by the Gram-negative bacterium Yersinia pestis routinely affects animals and occasionally humans, in the western United States. The strains native to the North American continent are thought to be derived from a single introduction in the late 19th century. The degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of North American plague are highly desired. To assay genetic diversity of plague isolates within confined geographic areas, draft genome sequences were generated by 454 pyrosequencing from nine environmental and clinical plague isolates. In silico assemblies of Variable Number Tandem Repeat (VNTR) loci were compared to laboratory-generated profiles for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels) were compared to previously sequenced Y. pestis isolates. The resulting panel of mutations allowed clustering of the strains and tracing of the most likely evolutionary trajectory of the plague strains. The sequences also allowed the identification of new putative SNPs that differentiate the 2009 isolates from previously sequenced plague strains and from each other. In addition, new insertion points for the abundant insertion sequences (IS) of Y. pestis are present that allow additional discrimination of strains; several of these new insertions potentially inactivate genes implicated in virulence. These sequences enable whole-genome phylogenetic analysis and allow the unbiased comparison of closely related isolates of a genetically monomorphic pathogen.

A Great Carolingian Panzootic: The Probable Extent, Diagnosis and Impact of an Early Ninth-Century Cattle Pestilence

Abstract: This paper considers the cattle panzootic of 809-810, the most thoroughly documented and, as far as can be discerned, spatially significant livestock pestilence of the Carolingian period (750-950 CE). It surveys the written evidence for the plague, and examines the pestilence’s spatial and temporal parameters, dissemination, diagnosis and impact. It is argued that the plague originated east of Europe, was truly pan-European in scope, and represented a significant if primarily short-term shock to the Carolingian agrarian economy. Cattle in southern and northern Europe, including the British Isles, were affected. In all probability, several hundreds of thousands of domestic bovines died, adversely impacting food production and distribution, and human health. A diagnosis of the rinderpest virus (RPV) is tentatively advanced.

Plague in Brazil: From Now and Then

Abstract: In Brazil, plague is a greatly neglected disease. It received some attention when it was first introduced in 1899 and again during the first decades of the twenty century, when it spread to important cities. Plague was forgotten as soon as it became restricted to isolated and poor areas, but it received renewed attention in the 1960s, when the lack of control resulted in increased plague-related morbidity and mortality. Records of this zoonosis are lacking, and the biotic and abiotic factors in the epidemiological chain are virtually unknown by the public health services and universities. However, the systematic detection of Yersinia pestis antibodies in sentinel animals has provided evidence of its continued presence and the possibility of its reemergence. In this paper, some aspects of plague epidemiology and plague control from 1899 to 2011 are described and analyzed. This information could support new studies of the natural history of plague in Brazil.

Plague Epidemic in the Kingdom of Naples, 1656–1658

Abstract: To the Editor: In 1656, an epidemic of plague occurred in the Kingdom of Naples, Italy. Earlier the disease had spread from Algiers to Spain; in June 1647, it appeared in Valencia, and in the spring of 1648, it appeared in Aragon and several other Spanish areas of Valencia, Andalusia, and Catalonia. In 1652, plague had spread to Sardinia and then to the cities and territories of Naples, Rome, and Genoa. Within the Kingdom of Naples, plague first reached the town of Naples in the spring of 1656. Despite measures restricting population movement, by the summer of 1656, the disease had reached several provinces in southern Italy (1,2). Historical records indicate that the epidemic in Barletta, in southern Italy, developed after the arrival of a ship from Naples. On May 26, 1656, the ship Sant’ Andrea arrived from Naples at the port of Barletta. However, after sanitary inspection, the ship was prevented from landing and obliged to depart, but this measure was not sufficient to prevent the disease from entering the port. The Barletta epidemic peaked in October, after which the number of cases diminished; and on June 22, 1657, Barletta was declared free of plague. Of this city’s original population of 20,000, the disease killed 7,000–12,000 persons. It is hypothesized that throughout the Kingdom, the plague killed ≈1,250,000 persons (1,2). Since the 14th century, noble families of Barletta had been buried in tombs in underground tunnels of Sant’ Andrea church. During restoration of the church in 2009, more underground tunnels containing many skeletons were discovered. It has been hypothesized that the church had also been used as a cemetery during the plague epidemic. During an inspection of the skeletons, 5 skulls of young persons were identified and collected. For a negative control, the skull of a person buried in a tomb before the epidemic was also collected. The skulls were radiographed to identify unerupted teeth (Figure), which were then aseptically extracted. After classification, each tooth was cut along a sagittal line to uncover the dental pulp, which was then hydrated in sterile phosphate-buffered saline (pH 7.2) for 48 h at 37°C. The DNA was extracted by using DNAeasy Blood and Tissue Kits (QIAGEN, Hilden, Germany) and by modifying the first step, which was conducted overnight at 56°C with 600 μL of ATL buffer (QIAGEN) and 50 μL of proteinase K. To verify the presence of inhibiting substance, the control DNA extracts were screened by using a PCR for human mitochondrial DNA (3). Figure Radiograph of skull found under Sant’ Andrea church in Barletta, Italy, in 2009, showing unerupted teeth (circled) that were later extracted aseptically. To investigate the cause of the deaths, we adopted a PCR suicide method and searched for Yersinia pestis. We amplified the pla gene for Y. pestis by using Sybr green PCR in real time with a modification of a previous protocol (4) coupled with conventional PCR according to Drancourt et al. (5). Conventional PCRs were adopted for Bacillus anthracis by targeting the pag and capC genes (6) and for Salmonella enterica serovar Typhi by targeting the narG gene (7). To prevent cross-contamination, we conducted all PCRs with a negative control and in the absence of positive controls. Melting curve analysis and agarose gel electrophoresis of PCR products indicated suspected positive samples. All amplicons relative to conventional and suicide PCR were submitted for sequencing analysis confirmation. The negative DNA was reanalyzed to confirm the results. From the 26 dental pulp samples analyzed from the 5 skulls of young persons, 7 samples were positive for the pla gene of Y. pestis by the Sybr green real-time PCR, and 2 of these were positive for this gene by conventional PCR. All were negative for B. anthracis and S. enterica ser. Typhi. GenBank BLAST (www.ncbi.nlm.nih.gov/blast/Blast.cgi) results of the 2 sequenced amplicons found a 100% match with the reference sequences (GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"AL109969.1","term_id":"5763810"}}AL109969.1); query coverage was 100%. The sequences obtained were deposited in the GenBank sequence database under accession nos. {"type":"entrez-nucleotide","attrs":{"text":"JN208020","term_id":"358250394"}}JN208020–1. In conclusion, the confirmed finding of DNA of Y. pestis in 2 skeletons and suspected finding in the remaining 3 suggests that these persons died of plague during the 1656–1658 epidemic in southern Italy. Although it has not been universally agreed upon, several studies have confirmed that the agent of 16th to 18th century “plague” epidemics in Europe were caused by Y. pestis. Different methods have documented Y. pestis as the agent in 10 Black Death burial sites scattered over 5 countries (8). In northern Italy, the presence of Y. pestis has been confirmed in Venice (14th–17th centuries) (8), Genoa (Bastione dell’Acquasola) (14th century) (9), and Parma (16th–17th centuries) (10). This study confirms that the plague that infected the Kingdom of Naples, which spanned almost all of southern Italy, was also caused by Y. pestis.