Article

Empirical “integrated disease management” in Ferrara during the Italian plague (1629–1631)

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Abstract

Plague, a highly infective disease caused by Yersinia pestis (Proteobacteria: Enterobacteriales), ravaged Europe from 1347 over the course of more than 450 years. During the Italian Plague (1629–1631), the disease was rampaging in the entire Northern Italy down to Tuscany, but the city of Ferrara was relatively spared, in spite that the economic activities were maintained with highly affected cities, such as Milan, through the relevant salt commerce. The aim of the study is to evaluate the hygiene rules that were effective in preventing the spread of the plague in Ferrara in 1630, by examining historical documents and reports. According to these documents, a kind of empirical “integrated disease management” was carried out, using remedies including compounds with bactericidal, anti-parasite and repellent activity, and by technical strategies including avoidance of possible plague carriers. The anti-plague remedies and technical strategies used in ancient Ferrara are critically analysed using a multidisciplinary approach (pharmaceutic, medical, epidemiologic and entomological) and compared to current prevention protocols.

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... [9]. In Ferrara, according to documentation from the Diocesan Historical Archives, the mortality rate in that period was 20 deaths per week [10], absolutely regular for 32,000 inhabitants ( Figure 1). ...
... From a preliminary study of Ferrara's documents, it emerged that Ferrara, already in the 16th century, had already understood that the spread of the plague contagion could occur through domestic animals including cats, pigs, chickens, dogs that carry the plague from one house to another [10]. These animals can host vectors such as human flea P. irritans (which may colonize short haired mammals such as pigs), Ctenocephalides felis (the fleas of cats), C. canis (dogs) and Synopsyllus fonquerniei (chickens). ...
... In Ferrara city, a sort of "integrated empirical management of the disease" was carried out, using remedies that included compounds with antiparasitic and repellent activity (galenic), and technical strategies that included the prevention of possible plague carriers [10]. Sanitization of the house, exposure to fire and sun, ventilation, temperature and humidity, are in fact effective in vector control [17,18]. ...
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The plague caused by the bacterium Yersinia pestis, provides one of the best historical examples of pandemic infection. It can therefore be considered the first "globalized" disease, thanks also to the crowds that favoured the rebalancing of infectious agents between Europe and the Middle East. In this paper we analyse all the official documents of the time, highlighting the most effective prevention measures implemented in the city of Ferrara during the Italian plague. Historical mortality data for the 1630 Italian plague in northern Italy are first analysed. In contrast to the high rates recorded throughout the area from Milan to Florence, the mortality rate in Ferrara remained normal over the period. From the city's documents it emerged that the authorities, from the 16th century onwards, had already understood that the spread of the contagion could also occur through domestic animals, although rats are never mentioned. The strength of Ferrara's response to the "plague emergency" stems from an efficient and emergency-ready health control system, financed and supported by the "permanent surveillance team of the city and the Pontifical Legation of Ferrara - Azienda Sanitaria Pubblica" even in times of great economic difficulty for the State. Among the various measures that the city of Ferrara adopted to deal with the plague the following should be mentioned: guards at the city gates, lazarettos, safety of doctors, self-isolation and treatment of every suspicious case as if it were a real case of plague, measures to support the poorer classes of the population, veterinary and hygiene standards for the city and for housing, management of Catholic religious functions and the precepts of the Legation of Ferrara, which was under papal control, closure of churches to avoid mass gatherings, and limitations of all kinds of social and economic relations within and outside the population. The broad regimen, laid down in the 16th century, contains extremely modern health rules which are very much in line with those recommended by the WHO and the health authorities of each individual state in the current COVID-19 pandemic, even starting with hand-washing. The fight against epidemics of the past, especially the history of the plague in the 17th century, anticipates very important and valid concepts, and represents a wake-up call for the recent epidemics of emerging pathogens.
... the study of the Black Death plague had a major impact on mainland europe as it killed at least one-third to two-thirds of the european population (Belich, 2016). in historical records, the Black Death plague is said to be a multiregional pandemic, this situation evidenced by the Black Death also occurring in most of asia and the Middle east (carmichael, 2006). as a result of the Black Death pandemic situation in the 1700s, there were several outbreaks in most parts of europe (cohn, 2008), namely the great plague of Milan (1629-1631) (Vicentini et al., 2020), the great plague of london (1665-1666) (Zell & Davies, 2022), the great plague of Vienna (1679) (laifle, 1937), and the great plague of Marseille (1720-1723) (Devaux, 2013). ...
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... The few cases, owing to strict laws and the rule of considering every suspected case as a plague and immediate isolation, enabled only the Lazaret of San Luca south of the city to be used. On the border of the Legation of Ferrara to the north and south Pontelagoscuro, Cento and Lugo (due to the relaxation of the measures) had numerous cases in the lazarets [7,1]. ...
... The curiosity of analysing the data, albeit limited to deaths, as there are no records of contagions, was to see if even in the case of the Spanish plague, although the city of Ferrara was not spared, it was less affected than other areas of the country. In our previous research, Ferrara was partially spared by the plague in the late 1500s and 1630s [32,33]. Today, it seems that COVID-19 during the first wave struck less violently in this city. ...
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This article aims to analyse the effects of plague on the long‐term development of Italian cities, with particular attention to the 1629–30 epidemic. By using a new dataset on plague mortality rates in 56 cities covering the period c. 1575–1700, an economic geography model verifying the existence of multiple equilibria is estimated. It is found that cities severely affected by the 1629–30 plague were displaced to a lower growth path. It is also found that plague caused long‐lasting damage to the size of Italian urban populations and to urbanization rates. These findings support the hypothesis that seventeenth‐century plagues played a fundamental role in triggering the process of relative decline of the Italian economies.
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Fleas are a monophyletic group that has evolutionary ties with the mecopteroid insect orders—namely, Mecoptera and Diptera. They are morphologically unique ectoparasites. There are approximately 2500 species and subspecies of fleas that are currently placed in 15 families and 220 genera. Flea classification is based almost exclusively on the chitinous morphology of cleared adult specimens. Adult fleas are small (1─8 mm), wingless, almost invariably, bilaterally compressed, and heavily chitinized. Fleas are holometabolous insects, with an egg, larval (typically consisting of three instars), and pupal stage. Fleas have evolved a plethora of specialized behaviors and ecologies to locate and exploit their hosts. Mating behavior in most fleas follows a distinct sequence of events. There are many fleas that are of medical-veterinary importance such as human flea, oriental rat flea, cat flea, European rabbit flea, and many more. Many species are annoying biters that can cause considerable discomfort, sometimes leading to secondary infections of bite wounds. The bites of some species can cause dermatitis or allergic reactions. Various methodologies are used to control fleas or to protect humans and other animals from flea bites that are frequent during vacuuming in homes, steam cleaning of carpets, treatment of flea-infested premises with various insecticides, personal protectants, and the use of ultrasonic repellent devices.
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In this paper, the chemical composition and biological activity of the essential oil of Artemisia absinthium was studied. The aim of this study was to investigate the potential of ethnopharmacological uses of this plant species in the treatment of gastrointestinal diseases and wounds, and as an insect repellent. The aerial part of the plant was hydrodistilled, and the chemical composition of the essential oil was analyzed by gas chromatography and gas chromatography/mass spectrometry. Forty-seven compounds, corresponding to 94.65 % of the total oil, were identified, with the main constituents being sabinene (24.49 %), sabinyl acetate (13.64 %), and α-phellandrene (10.29 %). The oil yield was 0.23 % (v/w). The antimicrobial activity of the oil was investigated against ten bacterial isolates (from patients wounds and stools) and seven American Type Culture Collection strains using a microwell dilution assay. The minimal inhibitory/bactericidal concentration of the oil ranged from < 0.08 to 2.43 mg/mL and from 0.08 to 38.80 mg/mL, respectively. The antioxidant activity of the essential oil was evaluated using 2,2-diphenyl-1-picrylhydrazil and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical-scavenging methods and assessed as significant. Skin irritation potential and acute toxicity of the oil were also investigated. Results of the skin irritant reaction showed that none of the 30 volunteers developed a positive skin irritant reaction to undiluted A. absinthium essential oil. Acute oral exposure to the essential oil did not cause mortality in the treated mice, but it did cause neurological, muscle, and gastrointestinal problems. A subchronic toxicity test on Drosophila melanogaster showed that the essential oil of A. absinthium is toxic for developing insect larvae. Starting with the concentration of 0.38 % of essential oil in medium, significant mortality of larvae exposed to the oil was noted when compared to the control. Probit analysis revealed that the LC50 value of A. absinthium essential oil for D. melanogaster larvae after 15 days of exposure was 6.31 % (49 mg/mL). The essential oil also affected the development of D. melanogaster larvae and significantly delayed achievement of the pupa stadium.
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The need for new antimicrobial agents is becoming one of the most urgent requirements in modern medicine. The venoms of many different species are rich sources of biologically active components and various therapeutic agents have been characterized successfully including antimicrobial peptides (AMPs). Due to their potent activity, low resistance rates and unique mode of action, AMPs have recently received much attention. This review focuses on AMPs from the venoms of scorpions and examines all classes of AMPs found to date. It gives details of their biological activities with reference to peptide structure. The review examines the mechanism of action of AMPs and with this information, suggests possible mechanisms of action of less well characterised peptides. Finally, the review examines current and future trends of scorpion AMP research, by discussing recent successes obtained through proteomic and transcriptomic approaches.
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The search for more eco-friendly acaricides has prompted testing of medicinal plants from botanical sources. To evaluate the eradication of house dust mites (HDM), Dermatophagoides pteronyssinus, by direct contact using the essential clove oil (Eugenia caryophyllus). A pilot study was initiated to determine the killing power of clove oil. Synthetic fibers were immersed in 2% clove oil for 30 min, dried in a hot air oven at 60°C for 2 hrs after which 0.5 gm of HDMs were exposed to these coated fibers placed in the Siriraj Chamber (SC). Two additional long-term methods were employed. Ten mites were placed in the SC and 10 μl of clove oil was pipetted or sprayed onto them. These latter two procedures were each carried out for 3 consecutive days at 0, 1, 3 and 6 months. The solutions antimicrobial and antifungal properties were evaluated by exposing common bacteria and fungi to sterile filter disks impregnated with the mixture, and after overnight incubation, the disc diffusion method on nutrient agar was used. Ethyl alcohol served as the placebo. 99% and 81%, respectively, while the placebo mortality was <5%. The zone of inhibition indicated significant clearance for all the bacteria and fungi indicating greater biocidal activity when compared to the controls. SEMs revealed dead mites on the fibers. The effectiveness of pipetting and spraying was 99% and 81%, respectively, while the placebo mortality was <5%. The zone of inhibition indicated significant clearance for all the bacteria and fungi indicating greater biocidal activity when compared to the controls. Clove oil is a promising agent for killing dust mites with a potential use in dust-mite laden mattresses. Spraying diminishes in efficiency after 3 months.
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Unlabelled: Insect-resistant films containing a microencapsulated insect-repelling agent were developed to protect food products from the Indian meal moth (Plodia interpunctella). Cinnamon oil (CO), an insect repelling agent, was encapsulated with gum arabic, whey protein isolate (WPI)/maltodextrin (MD), or poly(vinyl alcohol) (PVA). A low-density polyethylene (LDPE) film was coated with an ink or a polypropylene (PP) solution that incorporated the microcapsules. The encapsulation efficiency values obtained with gum arabic, WPI/MD, and PVA were 90.4%, 94.6%, and 80.7%, respectively. The films containing a microcapsule emulsion of PVA and CO or incorporating a microcapsule powder of WPI/MD and CO were the most effective (P < 0.05) at repelling moth larvae. The release rate of cinnamaldehyde, an active repellent of cinnamaldehyde, in the PP was 23 times lower when cinnamaldehyde was microencapsulated. Coating with the microcapsules did not alter the tensile properties of the films. The invasion of larvae into cookies was prevented by the insect-repellent films, demonstrating potential for the films in insect-resistant packaging for food products. Practical application: The insect-repelling effect of cinnamon oil incorporated into LDPE films was more effective with microencapsulation. The system developed in this research with LDPE film may also be extended to other food-packaging films where the same coating platform can be used. This platform is interchangeable and easy to use for the delivery of insect-repelling agents. The films can protect a wide variety of food products from invasion by the Indian meal moth.
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Unlabelled: Sandalwood oil has been found in numerous therapeutic applications in traditional medicines such as Chinese traditional medicine and Ayurveda. However, there are no comparative accounts available in the literature that focused on in vitro and in vivo tree sample-derived extracts. Combined dichloromethane and methanol extracts were obtained from in vitro samples, that is, callus, somatic embryo and seedlings, and in vivo from leaves of non-oil-yielding young and oil-yielding matured trees. Phytochemical evaluation of the extracts reveals that the tree is rich in terpenoids, saponin, phenolics and tannins. The antibacterial properties of the five extracts were compared with sandalwood oil by screening against nine Gram-negative and five Gram-positive bacterial strains by disc diffusion, agar spot and TLC bioautography methods. Minimum inhibitory concentration (MIC) for sandalwood oil was determined to be in the range of 0·078-5 μg ml(-1) for most of the test micro-organisms screened. Bioautography results indicated the presence of potential antimicrobial constituents in somatic embryo extracts and sandalwood oil. Among the extracts screened, the somatic embryo extracts showed the strongest antibacterial activity comparable only with sandalwood oil and matured tree leaves' extract. The findings presented here also suggest that apart from sandalwood oil, other parts of this tree across developmental stages are also enriched with antibacterial principles. Significance and impact of study: This study constitutes the first systematic investigation on phytochemical composition and antimicrobial efficacy of sandalwood tree across in vitro and in vivo developmental stages screened against thirteen bacterial strains by four methods. Using a battery of antimicrobial assay techniques, it is possible to follow the differential bioactive metabolic richness of plant parts, to decipher, for example comparable efficacy of somatic embryo extracts and sandalwood oil.
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In this study, the effects of Benzoinum and Styrax on Escherichia coli (E. coli) growth were investigated by microcalorimetry. Using a TAM Air Isothermal Calorimeter, ampoule method, the power-time curves of E. coli growth at 37°C affected by Benzoinum and Styrax were measured. By analysing some quantitative thermokinetic parameters, such as growth rate constants k, the maximum heat-out power Pm, the time of the maximum heat-out power tm, the total heat production Qt and inhibitory ratio I, one could find that low concentrations (0-3.9 mg mL(-1)) of Benzoinum and Styrax had stimulation effects on E. coli growth, and high concentrations (7.8-125.0 mg mL(-1)) of these two drugs would inhibit the growth of the bacteria. The antibacterial effects of Benzoinum and Styrax can also be expressed as half inhibitory concentration IC50. The IC50 values for Benzoinum and Styrax are 78.5 and 88.0 mg mL(-1), respectively, which suggests that the antibacterial effect of Benzoinum on E. coli was much stronger than that of Styrax. This study provides a useful method to investigate the effects of herbal medicines on microbes. It also supplies some references for the application of Benzoinum and Styrax in clinical treatment.
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Phospholipase A(2) (PLA(2)), a common toxic component of snake venom, has been implicated in various pharmacological effects. In this study, a basic myotoxic PLA(2), named EcTx-I was isolated from Echis carinatus snake venom by using gel filtration on Superdex G-75, and reverse phase HPLC on C18 and C8 Sepharose columns. PLA(2), EcTx-I was 13,861.72 molecular weight as estimated by MALDI-TOF (15 kD by SDS-PAGE), and consisted of 121 amino acid residues cross-linked by seven disulfide bonds. The N-terminal sequences revealed significant homology with basic myotoxic PLA(2)s from other snake venoms. The purified PLA(2) EcTx-I was evaluated (250 μg/ml) for bactericidal activity of a wide variety of human pathogens against Burkholderia pseudomallei (KHW&TES), Enterobacter aerogenes, Escherichia coli, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus. EcTx-I showed strong antibacterial activity against B. pseudomallei (KHW) and E. aerogenes among the tested bacteria. Other Gram-negative and Gram-positive bacteria showed only a moderate effect. However, the Gram-positive bacterium E. aerogenes failed to show any effect on EcTx-I protein at tested doses. The most significant bacteriostatic and bactericidal effect of EcTx-I was observed at MICs of >15 μg/ml against (B. pseudomallei, KHW) and MICs >30 μg/ml against E. aerogenes. Mechanisms of bactericidal and membrane damaging effects were proved by ultra-structural analysis. EcTx-I was able to induce cytotoxicity on THP-1 cells in vitro as well as lethality in BALB/c mice. EcTx-I also induced mild myotoxic effects on mouse skin, but was devoid of hemolytic effects on human erythrocytes up to 500 μg/ml. It is shown that the toxic effect induced by E. carinatus venom is due to the presence of myotoxic PLA(2) (EcTx-I). The result also corroborates the hypothesis of an association between toxic and enzymatic domains. In conclusion, EcTx-I displays a heparin binding C-terminal region, which is probably responsible for the cytotoxic and bactericidal effects.
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Acetic acid has been commonly used in medicine for more than 6000 years for the disinfection of wounds and especially as an antiseptic agent in the treatment and prophylaxis of the plague. The main goal of this study was to prove the suitability of acetic acid, in low concentration of 3%, as a local antiseptic agent, especially for use in salvage procedures in problematic infections caused by organisms such as Proteus vulgaris, Acinetobacter baumannii or Pseudomonas aeruginosa. This study was designed to compare the in vitro antimicrobial effect of acetic acid with those of common local antiseptics such as povidone-iodine 11% (Betaisodona), polyhexanide 0.04% (Lavasept), mafenide 5% and chlohexidine gluconate 1.5% cetrimide 15% (Hibicet). Former studies suggest the bactericidal effect of acetic acid, but these data are very heterogeneous; therefore, a standardised in vitro study was conducted. To cover the typical bacterial spectrum of a burn unit, the following Gram-negative and Gram-positive bacterial strains were tested: Escherichia coli, P. vulgaris, P. aeruginosa, A. baumannii, Enterococcus faecalis, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA) and beta-haemolytic Streptococcus group A and B. The tests showed excellent bactericidal effect of acetic acid, particularly with problematic Gram-negative bacteria such as P. vulgaris, P. aeruginosa and A. baumannii. The microbiological spectrum of acetic acid is wide, even when tested at a low concentration of 3%. In comparison to our currently used antiseptic solutions, it showed similar - in some bacteria, even better - bactericidal properties. An evaluation of the clinical value of topical application of acetic acid is currently underway. It can be concluded that acetic acid in a concentration of 3% has excellent bactericidal effect and, therefore, seems to be suitable as a local antiseptic agent, but further clinical studies are necessary.
Article
The antimicrobial activity of extracts of Curcuma zedoaria and Curcuma malabarica tubers was tested against six bacterial and two fungal strains using the agar well diffusion and broth dilution methods. Petroleum ether, hexane, chloroform, acetone and ethanol extracts exhibited antibacterial as well as antifungal activity. Acetone and hexane extracts of both tubers showed comparable antimicrobial activity as indicated by minimum inhibitory concentration (MIC) values, but other extracts of Curcuma malabarica showed significantly lower activity than those of Curcuma zedoaria. The MIC values for different strains and extracts ranged from 0.01 to 0.15 mg/ml in Curcuma zedoaria and from 0.01 to 0.94 mg/ml in Curcuma malabarica. Staphylococcus aureus (Gram positive) was inhibited by Curcuma malabarica but not by Curcuma zedoaria. This study is the first report of the antimicrobial properties of Curcuma malabarica. The findings also support the use of Curcuma zedoaria tubers in traditional medicine for the treatment of bacterial and fungal infections.
Article
Nutmeg (Myristica fragrans) is used in food preparations for its aromatic flavor. The present investigation was undertaken to evaluate the antibacterial activity of constituents of M. fragrans seeds. Seeds of M. fragrans were powdered and extracted with chloroform to obtain trimyristin, which on saponification yielded myristic acid. The mother liquor remaining after separation of trimyristin was concentrated and column-chromatographed with petroleum ether to separate myristicin. Antibacterial activity of these isolated constituents was evaluated by determination of minimum inhibitory concentration against selected Gram-positive and Gram-negative organisms. All the constituents isolated from nutmeg exhibited good antibacterial activity. This study shows the potential of natural compounds in replacement of synthetic preservatives.
Seasonal fluctuations of small mammal and flea communities in a Ugandan plague focus: evidence to implicate Arvicanthis niloticus and Crocidura spp. as key hosts in Yersinia pestis transmission
  • Moore
Ferrara dei Censimenti, Servizio statistico nazionale
  • A A Vv
Excursus sull'organizzazione dell'assistenza in tempi di pestilenza
  • Sabbatani
Rodent reservoirs and flea vectors of natural foci of plague
  • Gratz