Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria.

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.

"The blinding disease". The history of trachoma in Italians between the 19th and 20th centuries: colonial or national blindness?

Trachoma is one of the oldest known causes of blindness in humans and it is caused by the intracellular Gram-negative bacterium Chlamydia trachomatis serovars A, B, Ba and C. Its transmission has historically been related to poorness, overcrowded housing and scarce hygiene. We have traced the history of trachoma in Italy in the 19th and 20th centuries, among people living in Italy, those who immigrated to America and the population in the colonies, with a focus on Libya (1912-1943). Trachoma knowledge and perception in Italy and in its colonies was ambiguous during the 19th and 20th centuries. Trachoma was responsible for a great morbidity on both sides of the Mediterranean, in Italy as well as in Libya. Trachoma is still one of the leading infectious causes of preventable blindness worldwide and it was widespread in Italy and the Italian colonies in the first half of the last century.

The current state of knowledge on dracunculiasis: a narrative review of a rare neglected disease.

Dracunculiasis (Guinea Worm Disease) is a chronic disease that is primarily found in the arid and poor areas of our planet where water supply systems consist of open wells. This parasitic disease is transmitted to humans not only through the consumption of water contaminated with crustaceans harbouring larvae of Dracunculus medinensis, but also through the ingestion of paratenic (frogs) or transport hosts (fish). The natural progression of the disease is caused by adult worms invading connective tissues, leading to blistering and ulceration of the extremities, approximately one year after infection. In 1986, the Guinea Worm Eradication Program (GWEP) was launched and since then, the incidence of the disease has been reduced by over 99%. Indeed, the most recent global report from 2022 shows only 13 cases of human dracunculiasis worldwide, the lowest annual incidence ever reported. The new found knowledge of potential animal reservoirs and the recent discovery of possible edible paratenic hosts could pose challenges to the future eradication of this debilitating disease. Therefore, attempts to eradicate this parasitosis should not be postponed. Intensive research is needed in this neglected area of medicine, now that the goal is within reach.

Identification of IncA Plasmid, Harboring blaVIM-1 Gene, in S. enterica Goldcoast ST358 and C. freundii ST62 Isolated in a Hospitalized Patient.

In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast ST358 (O:8 (C2-C3) serogroup), sequenced by the MiSeq Illumina system, showed the presence of ß-lactamase genes (blaVIM-1, blaSHV-12 and blaOXA-10), aadA1, ant(2″)-Ia, aac(6')-Iaa, aac(6')-Ib3, aac(6')-Ib-cr, qnrVC6, parC(T57S), and several incompatibility plasmids. A wide variety of insertion sequences (ISs) and transposon elements were identified. In C. freundii TS3, these were the blaVIM-1, blaCMY-150, and blaSHV-12, aadA1, aac(6')-Ib3, aac(6')-Ib-cr, mph(A), sul1, dfrA14, ARR-2, qnrVC6, and qnrB38. IncA plasmid isolated from E.coli/K12 transconjugant and C. freundii exhibited a sequence identity >99.9%. The transfer of IncA plasmid was evaluated by conjugation experiments.

Modelling antimicrobial resistance transmission to guide personalized antimicrobial stewardship interventions and infection control policies in healthcare setting: a pilot study.

Infection control programs and antimicrobial stewardship have been proven effective in reducing the burden of diseases due to multidrug-resistant organisms, but quantifying the effect of each intervention is an open issue. For this aim, we propose a model to characterize the effect of interventions at single ward level. We adapted the Ross-Macdonald model to describe hospital cross-transmission dynamics of carbapenem resistant Klebsiella pneumoniae (CRKP), considering healthcare workers as the vectors transmitting susceptible and resistant pathogens among admitted patients. The model parameters were estimated from a literature review, further adjusted to reproduce observed clinical outcomes, and validated using real life data from a 2-year study in a university hospital. The model has been further explored through extensive sensitivity analysis, in order to assess the relevance of single interventions as well as their synergistic effects. Our model has been shown to be an effective tool to describe and predict the impact of interventions in reducing the prevalence of CRKP colonisation and infection, and can be extended to other specific hospital and pathological scenarios to produce tailored estimates of the most effective strategies.

Dracunculiasis over the centuries: the history of a parasite unfamiliar to the West.

Dracunculiasis (Guinea Worm Disease) is a terrible disease limited, even historically, to the arid and poor areas of our planet and which in the West has always been seen as an exotic disease and therefore has never taken root in the collective imagination. This parasitosis is transmitted to humans by drinking water contaminated with crustacean harboring larvae of Dracunculus medinensis, a nematode. The natural history of the disease is caused by adult worms invading connective tissues and causing blistering, ulceration and edema. Well known in Ancient Egypt where the disease was endemic in its southern area, was known in Europe mainly from the reports of medical writers starting from the Roman imperial period but without direct knowledge. In Middle age the descriptions of this disease that physicians and surgeons could read on medical books, at the end, were attributed to veterinary parasitic disease. In Modern age only during the colonialist era dracunculiasis was perceived as a problem, however sporadic. In 1986 Guinea Worm Eradication Program (GWEP) was launch without success. Thus, the disappearance of this parasitosis should still be postponed but not abandoned.

Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life.

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multivariable logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (a woman aged 96 years) was unvaccinated and the other (a woman aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals-Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) or Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a slightly stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥5 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of COVID-19 antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST.

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

The history of Gin and Tonic; the infectious disease specialist long drink. When gin and tonic was not ordered but prescribed.

Winston Churchill statement promoting Gin and Tonic as a life saver during British Empire extension hides many truths. As a matter of fact, the modern cocktail is thought to be born in India where it was widely distributed by Royal Navy for its anti-malarial properties. The aim of the present work is to review and unveil the history of Gin and Tonic through the centuries. As a matter of facts, primitive Gin and Tonic protective effects were well understood by physicians far before the advent of the "germ theory" and its fortunate invention is one of the most fascinating approaches in the history of preventive medicine. Indeed, quinine, a compound with protective effects on the replicative cycle of Plasmodium spp was discovered in 18th Century and since 19th it become the main compound of tonic beverages such as Schweppe's ones. Interestingly, it was administered to British expatriates' seamen and soldiers in order to prevent febrile paroxysms. Soon after, British military doctors demonstrated that the addition of lime or lemon peels to tonics was effective in preventing scurvy. While, addition of alcoholic beverages and gin contributed to make more enjoyable the bitter and unpleasant taste of this beverages. Results: The spectacular voyage of Gin and Tonic teaches us that a popular recreational drink of our Century was a powerful prophylaxis which certainly helped British colonial expansion.

Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab.

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild-moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.

Antimicrobial Use in Hospitalised Patients with COVID-19: An International Multicentre Point-Prevalence Study.

Studies suggest that the incidence of coinfections in patients with the coronavirus disease 2019 (COVID-19) is low, but a large number of patients receive antimicrobials during hospitalisation. This may fuel a rise in antimicrobial resistance (AMR). We conducted a multicentre point-prevalence survey in seven tertiary university hospitals (in medical wards and intensive care units) in Croatia, Italy, Serbia and Slovenia. Of 988 COVID-19 patients, 521 were receiving antibiotics and/or antifungals (52.7%; range across hospitals: 32.9-85.6%) on the day of the study. Differences between hospitals were statistically significant (χ2 (6, N = 988) = 192.57, p < 0.001). The majority of patients received antibiotics and/or antifungals within 48 h of admission (323/521, 62%; range across hospitals: 17.4-100%), their most common use was empirical (79.4% of prescriptions), and pneumonia was the main indication for starting the treatment (three-quarters of prescriptions). The majority of antibiotics prescribed (69.9%) belonged to the "Watch" group of the World Health Organization AWaRe classification. The pattern of antimicrobial use differed across hospitals. The data show that early empiric use of broad-spectrum antibiotics is common in COVID-19 patients, and that the pattern of antimicrobial use varies across hospitals. Judicious use of antimicrobials is warranted to prevent an increase in AMR.

The Italian lazarets of the Adriatic Sea: from their institution to the fight against the economic and demographic collapse caused by epidemics.

Since antiquity, with the growth of the human population and the expansion of nuclei of people (aggregations), infectious diseases have been a constant presence which decisively changed the course of history. The word "lazaret", meaning hospital for the hospitalization and treatment of plague victims and later, also leprosy, is Venetian. It was coined in the 14th century, and was exported to the world; it is still in use although it has slightly modified its meaning: "hospital in general, and shelter for infectious diseases". Lazarets perhaps arose from the overlapping and crossing of the name Nazareth associated with Lazarus, protector of leprosy patients and from other contagious diseases in general. The island of "Lazzaretto Vecchio", overlooking the Lido di Venezia, was named Isola di Santa Maria di Nazareth before the 15th century. However, the first city to take an official step in this direction was the Republic of Ragusa (Croatia), a city-state and flourishing Maritime Republic which was a trading pivot between the Ottoman Empire and the West. In 1377, for the first time in history, the city established a thirty-day quarantine on the three uninhabited islands of Mrkan, Bobara and Supetar for people arriving from infected places. The Republic of San Marco (Venezia) devised one of the oldest and most far-sighted sanitary solutions to contain the spread of the plague: a lazaret, or sanitary model of isolation and treatment that spread, with the name radiating from Venice, around the world. Venetian lazarets were the site of the Republic's innovative strategy to prevent and combat the plague, not only by isolating people for quarantine and goods from infected countries, but also by implementing complex procedures of 'contumacy and purgation' that required a constant investment of economic resources and slowed down traffic. Venice's governors quickly realized that spending money to prevent and fight the plague in lazarets was the only way to counter the economic and demographic collapse caused by epidemics. In the wake of the Venetian and Ragusian lazarets, Trieste also established its first lazaretto in 1717. This was because ships laden with goods from the Near East began to arrive in the city, and this new situation necessitated the adoption of a regulation of contumacy and the construction of a lazaret. This study aims to bring light to the main lazarets over the centuries, particularly those in the Ferrara district and those located in the upper Adriatic Sea, such as Trieste and other neighbouring cities built to fights pandemics.

COVID-19 and Spanish flu-18: review of medical and social parallelisms between two global pandemics.

The intrusion of infectious diseases in everyday life forces humans to reassess their attitudes. Indeed, pandemics are able catalyze rapid transitions in scientific knowledge, politics, social behaviors, culture and arts. The current Coronavirus diesease-19 (COVID-19) outbreak has driven an unprecedented interest toward the influenza pandemic of 1918. The issue is whether history can shed light on the best preventive response and future scenarios. The aim of this review is to highlight the parallelism between the two pandemics. Starting from epidemiology and clinical features, but further focusing on social and cultural issues, it is possible to unreveal great similarities. Their outbreak pattern lead to hypothesize a similar duration and death burden in absence of effective vaccines or innovative treatments for COVID-19. Thus, then as now, preventive medicine represents the first and most effective tool to contain the course of the pandemic; being treatments available only supportive. At the same time,both pandemics shared the same pattern of narration (e.g. scapegoating) and the same impact on minorities in high-income countries. Furthermore, visual art responded to pandemic issues in 2020 in the form of Graffiti art, while similar role was ruled by Expressionism movement during the Spanish flu. Photography also was capable to document both catastrophic scenarios. Thus, it is possible to find a lot of clinical and social similarities between the two pandemics. Nevertheless, if the Spanish flu was not unforseen, COVID-19 spillover was partially predictable and its global impact will hopefully not be overshadowed by a major crisis such as World War I.

The avid eaters of lives. New and old infectious diseases in Italy at the time of World War I: a historical overview of military medicine and public health.

World War I hit Italy from different perspectives. The one here described under an historical point of view regards the health of military and civil population, with a special focus on infective diseases. The 20th Century was the fuse of degeneration and eugenetics theories; which grew in the melée of war and technological innovation. Indeed, war is interestingly depicted as an entity capable of emphasizing the differences between those who wore a uniform and those who did not. As a matter of fact, some infections spared the civilian population while others felt with greater vengeance on this subgroup. Moreover, the incidence of different feared diseases was brought back to the rates of the late 19th Century. Thanks to a statistician, Giorgio Mortara (1885-1967) the impact of infective diseases in Wolrd War I on Italian demography is well established. Moreover, different military and civilian sources contribute to enrich the picture of the consequences of war. In conclusion World War I could see considered as a litmus paper. The litmus paper of successes and failures of italian public health management to face new medical challenges exacerbated by the crisis.

El Alamein: the battle in the battle. How infectious disease management changed the fate of one of the most important battle of the World War II.

El Alamein, on Egypt's Mediterranean coast, was the theater of war for one of the most important and decisive battles of the Second World War. The Allied victory in November 1942 opened the end of the Western Desert Campaign. The battle revived the morale of the Allies, being the first big success against the Axis since Operation Crusader in late 1941. The German threat to Egypt, the Suez Canal and the Middle Eastern and Persian oil fields was eliminated and the doors for Mediterranean advance were opened. Fighting in the desert under extreme human conditions exposed all the involved armies to health hazards going beyond those arising from common battle injuries. The outcome of the battle was influenced by a gap in morbidity and mortality derived from different approaches in infectious disease management between armies. The attention of the British for medical research, pharmacological experimentation, hygiene strategies and prevention may have been as important as warfare strategies in deciding the fate of the battle. Examples of some of these advances include wound nursing, control of endemic diseases, surveillance of difficult hygienic conditions, prevention of faecal-oral transmission diseases. During El Alamein Battle soldiers on both fronts where engaged in two wars: the first one, vertical, was against the enemy uniform; the second one, horizontal, was against invisible enemies called pathogens. Only surviving the horizontal war meant preserve enough units and morale in order to win El Alaman Battle.

Correlation between antibiotic consumption and resistance of bloodstream bacteria in a University Hospital in North Eastern Italy, 2008-2014.

PURPOSE: The spread of multidrug-resistant bacteria is a worrisome problem worldwide. This study investigated the correlation between antibiotic consumption and antimicrobial resistance trends of the most important bacteria causing bacteremia at the University hospital of Trieste, Italy, from 2008 to 2014. METHODS: Antibiotic consumption (Defined Daily Dose-DDD-per 100 patient/days) and antibiotic resistance (percentage of antibiotic intermediate o resistant isolates) were analyzed independently with linear correlation by year. Potential correlations between antibiotic consumption and bacteria resistance rates were investigated through the Pearson's correlation. RESULTS: The overall consumption of antibiotic grew from 80 to 97 DDD 100 patient/days (p = 0.005) during the study period. The increased consumption of amoxicillin/clavulanate and piperacillin/tazobactam was associated with the reduction of MRSA rate from 48.5 to 25.9% (p = 0.007 and p = 0.04, respectively). The increased consumption of piperacillin/tazobactam was associated with the reduction of ESBL-positive Enterobacteriaceae rate from 28.9 to 20.9% (p = 0.01). The increased consumption of carbapenems was associated with the increased rate of carbapenem-resistant Acinetobacter baumannii from 0 to 96.4% (p = 0.03). No carbapenem-resistant Enterobacteriaceae isolates were reported. The consumption of vancomycin grew significantly (p = 0.005). A dramatic spread of vancomycin-resistant Enterococcus faecium occurred in 2014. The consumption of fluoroquinolones and extended-spectrum cephalosporins remained stable. CONCLUSIONS: An antibiotic stewardship program targeted to limit the consumption of extended-spectrum cephalosporins and fluoroquinolones in favor of amoxicillin/clavulanate and piperacillin/tazobactam correlates with a decreasing rate of MRSA and ESBL-positive Enterobacteriaceae. The analysis of correlations between antibiotic consumption and bacterial resistance rates is a useful tool to orient antimicrobial stewardship policies at local level.