The rationale for a multi-step therapeutic approach based on antivirals, drugs and nutrients with immunomodulatory activity in patients with coronavirus-SARS2-induced disease of different severities.

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.

Cytokine storm in aged people with CoV-2: possible role of vitamins as therapy or preventive strategy.

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.

The Bolognese surgeon Giuseppe Ruggi: how and why the aseptic surgery was introduced in Bologna in the middle half of the XIX century.

BACKGROUND: The first reliable statistic data about perioperatory mortality were published in 1841 by the French Joseph-Francois Malgaigne (1806-1863): he referred to a mean mortality of 60% for amputations and this bad result was to be attributed mainly to hospital acquired diseases. The idea of "hospital acquired disease" although vague, included five infective nosologic entities, which at that time were diagnosed more frequently: erysipelas, tetan, pyemia, septicemia, and gangrene. Nonetheless, the suppuration with pus production was considered from most of the surgeons and doctors of that time as a necessary and unavoidable step in the process of wound healing. During the end of the eighteenth century, hospitals of the main European cities were transforming into aggregations of several wards, where the high concentration of patients created poor sanitary conditions and a consistent increase of perioperatory mortality. In 1865, Lister applied his first antiseptic dressing on the surface of an exposed fracture. These experimental attempts lead to an effective reduction of wound infections respect to the dressing with strings used previously. DISCUSSION: Lister's innovations in the field of wound treatment were based on two brand new concepts: germs causing rot were ubiquitarious and the wound infection was not a normal step in the process of wound healing. The concept of antisepsis was hardly accepted in the European surgical world: "Of all countries, Italy is the most indifferent and uninterested in experimenting this method, which has been so favorably judged from the greatest surgical societies in Germany". This quotation from the young surgeon Giuseppe Ruggi (1844-1925) from Bologna comes from his article where he presented his first experiences on aseptic medications started the previous year in the Surgical Department of Maggiore Hospital in Bologna. In his report, Ruggi described the adopted technique and suggested that the medication should be extended to all the surgical patients of the hospital:"… this is needed to totally remove from the hospital all those elements of infection which grow in the wounds dressed with the old method". The experimentation of this new dressing for the few treated cases was rigorous and concerned both the sterilization of surgical tools with the fenic acid (5%) and the shaving of the skin. Ruggi also observed that there was no correlation between the seriousness of the wound and its extension or way of healing: when "simple" cases that "should heal without complication" showed fever he often realized that "it was often due to a medication performed without following the rules for an accurate disinfection and dressing". Ruggi thought that the fever was connected to "reabsorption of pyrogenic substances, which can be removed cleaning and disinfecting the wound" in cases of wounds not accurately dressed and rarely medicated. Frequent postoperative medications of the wound were able to eliminate the fever within 2 h. Ruggi's attitude toward the fine reasoning lead him to introduce the concept of immunodeficiency related to physical deterioration: "… patients treated for surgical disease may sometimes suffer from complications of medical conditions, which initially escape the most accurate investigations… The surgical operation could, in some cases, hold the balance of power". CONCLUSIONS: The obtained results, published in 1879, appear extremely interesting. As he wrote in 1898, for the presentation of his case record of more than 1000 laparotomies, he had started "… operating as a young surgeon without any tutor, helped only by his mind and what he could deduce from publications existing at the moment …".

Figurative aspects suggestive of infectious diseases in the ceramic pots of the pre-Columbian Moche culture. Analysis of the ceramics collection in the Larco Museum of Lima, Peru.

The historical-medical and anthropological studies, regarding Mesoamerica and South America, have been mainly focused on the great empires (Inca, Atzec, Maya), while other civilizations have been less investigated and only recently are gaining interest. In general, the paleopathological research provides interesting data to know the type of nutrition and the general environmental conditions as well as to point out some ritual mutilation practices, which were relatively frequent in the pre-Columbian cultures. A lot of civilizations flourished in the South America before the arrival of the Spanish Conquistadores in the new world. In the last years it is progressively increasing the interest for the study of the Moche culture as well as for a deeper knowledge of pathocenosis of infectious diseases in the Moche society. Human infectious diseases are known to have a frequent animal origin, in particular from domesticated species, although the species domesticated in the pre-Columbian era were a small number. The purpose of our paper has been to examine the archeological findings suggestive of infectious diseases in artistic ceramic pots, dating back to the Moche period. We examined the iconography of ceramic pots belonging to the collection of the Larco Museum in Lima and reproducing body signs suggestive of infectious diseases. We identified 8 handworks with very interesting features by a medical point of view. In these handworks there are signs and lesions possibly associated with infectious diseases: risus sardonicus, orbital edema, facial nerve palsy, dorsal kyphosis, face and skin lesions. These features are compatible with some infectious diseases, including: syphilis, Bartonella bacilliformis, leishmaniasis, Pott's disease and Chagas disease. A wide discussion about these handworks is provided.

The plague which hit the city of Bologna in the year 1630.

In the year 1630, similarly to other cities of Northern Italy, Bologna was affected by a plague epidemic. It occurred after the arrival of Lansquenet troops, engaged by the Emperor Frederick II in the siege of Mantua city. The human losses have been calculated by the historian demographer Bellettini in the terms of around 15,000 people, so that the number of inhabitants in Bologna declined from 62,000 to 47,000 units in the time span of 7-8 months. Initially, during the winter and the early spring, although the plague epidemic had been known after that it involved many cities close to Bologna (i.e. Turin, Milan, Venice, Genoa and Verona), the population tried to keep the epidemic hidden, being afraid that commerce exchanges could be affected by this event. Later, starting from the month of May, under the guidance of cardinal Bernardino Spada, cooperating with the numerous religious orders and in particular with the one of the Camillians, the city reacted, launching an organization effort which significantly aided in the containment of the plague epidemic. A number of Lazarettos were organized outside of the city walls and relevant sums supported the clean operation of over 3,000 houses. The city Senate sustained the poor population with a sum of 700,000 lire and grain donations. Even if the loss of human lives was high, it resulted not so dramatic, compared with that paid by other Italian cities. From a cultural point of view, according to the belief of the scientific knowledge of that time, the miasmatic theories were still considered satisfactory, although in the common practice the people who could leave the city escaped from Bologna, in order to avoid the contagion. We can argue that the impact of the epidemic was reduced by means of the organizational approach with strict isolation measures for sick persons, the closing of the city walls in the urban areas more affected by the plague, and finally a sanctionatory and punitive approach for individuals, who disregarded the applied rules.

Malaria infection and human evolution.

During the evolution of the genus Homo, with regard to the species habilis, erectus and sapiens, malaria has played a key biological role in influencing human development. The plasmodia causing malaria have evolved in two ways, in biological and phylogenetic terms: Plasmodium vivax, Plasmodium malariae and Plasmodium ovale appear to have either coevolved with human mankind, or encountered human species during the most ancient phases of Homo evolution; on the other hand, Plasmodium falciparum has been transmitted to humans by monkeys in a more recent period, probably between the end of the Mesolithic and the beginning of the Neolithic age. The authors show both direct and indirect biomolecular evidence of malarial infection, detected in buried subjects, dating to ancient times and brought to light in the course of archaeological excavations in major Mediterranean sites. In this review of the literature the authors present scientific evidence confirming the role of malaria in affecting the evolution of populations in Mediterranean countries. The people living in several different Mediterranean regions, the cradle of western civilization, have been progressively influenced by malaria in the course of the spread of this endemic disease in recent millennia. In addition, populations affected by endemic malaria progressively developed cultural, dietary and behavioural adaptation mechanisms, which contributed to diminish the risk of disease. These habits were probably not fully conscious. Nevertheless it may be thought that both these customs and biological modifications, caused by malarial plasmodia, favoured the emergence of groups of people with greater resistance to malaria. All these factors have diminished the unfavourable demographic impact of the disease, also positively influencing the general development and growth of civilization.

[Emerging and spread of the fifth Plasmodium spp. pathogenic for human malaria: Plasmodium knowlesi]. / L'emergere e la diffusione del quinto plasmodio della malaria patogeno per l'uomo: Plasmodium knowlesi.

The beginning of the third millennium has been characterized by the emerging and progressive characterization of a novel malaria Plasmodium pathogen of simian origin (Plasmodium knowlesi), which now represents the fifth human malaria parasite. Evolutionary, environmental, and diagnostic-clinical features are briefly outlined on the ground of the most recent literature evidences.

The destiny of Italian prisoners in Austro-Hungarian POW camps during the First World War: remembering the defeat of Caporetto 100 years on.

The living conditions of Italian prisoners during the First World War were extremely difficult. At the end of the conflict, the treatment of Italian soldiers in Austro-Hungarian POW camps and in those of the German territories was recognized as particularly harsh in comparison with that of other prisoners. The reasons may be ascribed to three main factors. The Italian prisoners paid the price of being considered traitors, since Italy was allied with the Austro-Hungarian Empire and with Germany until 1914, subsequently switching to the side of France, the United Kingdom and Russia. The Italian government and the Italian High Command considered their soldiers poorly inclined to engage in a war which became over time increasingly costly in terms of human sacrifice. The strategy pursued by the General-in-Chief Luigi Cadorna was very aggressive and showed little care for the life conditions of his troops, who were frequently thrown into the fray and exposed to potential slaughter. Due to this negative judgement on their troops' willingness to fight, the government did not help, and even hindered, the despatch of packages of food and clothes to prisoners in the Austro-Hungarian and German camps via the Red Cross. The idea of a better life in the trenches compared with that expected in the camps as prisoners was widespread. Thirdly, the maritime blockade of the Adriatic Sea over time reduced to starvation the populations of Austria, Hungary and Germany, which obviously had grave repercussions on prisoners. It was estimated that around 100,000 Italians lost their lives in POW camps; after the defeat at Caporetto, when over 250,000 prisoners were captured, the number of deaths rose. The main causes of death were: tuberculosis, pneumonia, malnutrition and typhoid fever. At the end of the war, when coming back to Italy, former POWs were interned for months in camps (located predominantly in the Emilia region) and had to face interrogation and trials to demonstrate they were not deserters and were free to go back home. In the meantime, many lost their lives due to "Spanish" flu, pneumonia and other infectious diseases. Only the mobilization both of families and public opinion forced the Italian government to close the camps at the end of the year 1919.

The plague in Bologna in the year 1527.

In the year 1527, following the invasion of Italy by Landsknechts, who were headed by Georg von Frundsberg, the bubonic plague appeared in the country. These soldiers were part of an army that Charles V sent to invade Italy in order to subjugate the Italian states which had adhered to the League of Cognac. In Bologna during the year 1527 believers held a procession from the Sanctuary of the Madonna del Soccorso, through the city, as far as the Church of San Rocco. The reason for this practice was linked with the plague epidemic. After some cases of plague observed in the Borgo di San Pietro district the miracle of the interruption of the epidemics, thanks to the intervention of Our Lady, was narrated by the faithfuls. Later, after several decades, it was reported by several authors from Bologna, who were not witnesses to the facts, that the epidemic had involved 12,000 out of a total population of around 60,000 inhabitants at that time. We re-evaluated this situation starting from the demographic data concerning the citizens in Bologna during the 15th, 16th and 17th centuries. Furthermore, we performed a search in the State Archives in the city of Bologna in order to find any public notices from the city authorities in the year 1527 aiming to counteract a plague epidemic. Our investigation found no elements to support the outbreak of this disease. Throughout the 16th century, until 1590, the population grew significantly, and no public notices were issued or specific laws enacted to deal with the plague until the year 1557. However, it remains possible that in the area in question, some episodes of plague occurred, but it was fortunately a micro-epidemic, which involved a very poor area of the city. Then this disease was self-limited. However, in our opinion, this episode proved very important, since in this district of Bologna, and around a wooden image of the Madonna del Soccorso, a confraternity took place, and its activities continued until the year 1798. This group of citizens also played a major role in many charitable activities to aid the inhabitants of Bologna, during a difficult historical period, namely the Protestant Reformation, and contributed to strengthen the faith of Catholic believers.

The health of Italian troops and prisoners during World War I.

During the Great War, which involved Italy from May 1915 until November 1918, the Italian Army paid an extremely high price in terms of suffering; around 600,000 soldiers died. About 100,000 of these deaths were caused by diseases, mainly infectious ones. The casualties accounted for over one million cases. Epidemics of cholera and petechial typhus were recorded as well as an increase in morbidity due to tuberculosis and malaria, which had shown some minor epidemiological reduction in several regions of Italy during the years preceding the Great War. A large number of soldiers acquired respiratory tract and brain infections. Severe limb infections were due to war wounds, but also to a novel disorder called "trench foot", In a context of general hygienic decay, death and stress linked to massive bombing, severe psychiatric disorders were observed. They were called "shell shock" in English (and known in Italy as "the wind of the howitzer"). The patients suffering from the above psychiatric disorders were considered simulators by the great majority of psychiatrists, who largely believed such soldiers wanted to avoid active combat. They were subjected to electric shocks and later sent back to the war front or to a mental hospital in the most severe cases. In some dramatic occurrences, like at the time of the Caporetto defeat, a substantial number of soldiers were dealt rough justice in front of firing squads under the suspicion of desertion. Yet World War I, with its dramatic load of suffering, forced the medical environment to develop extremely innovative techniques and research applied to clinical practice. During the decades to follow, such efforts yielded major results in the field of pharmacology: studies which led to the discovery of the first antibiotics were set in motion.

Plagues and artistic votive expressions (ex voto) of popular piety.

In past centuries, epidemics, the scourge of humankind, caused pain, anger, uncertainty of the future, social as well as economic disorder and a significant impact on their victims, involving also their spiritual sphere. The latter effect led to undoubted effects on participation in the religious and social life of communities. The custom of preparing artistic votive expressions has been lost in the mists of time and evidence of ex voto gifts, offered by believers to pagan gods, has been found in prehistoric archaeological sites. Furthermore, several finds from the Ancient Greek and Roman worlds may be observed in our museums. These remains are generally ceramic and metal artifacts, reproducing limbs and other body parts which had been healed. These elements, according to the belief of those making the offerings, had benefited from the miraculous intervention of a thaumaturgical deity. With the advent of Christianity, some pre-existing religious practices were endorsed by the new religion. Believers continued to demonstrate their gratitude in different ways either to miracle-working saints or to the Virgin Mary, because they thought that, thanks to an act of faith, their own health or that of a family member would benefit from the direct intervention of the divine entities to whom they had prayed. In the Ancient Greek world, it was believed that the god Asclepius could directly influence human events, as testified by the popularity of shrines and temples to the god, especially at Epidaurus. In the Christian world as well, particular places have been detected, often solitary and secluded in the countryside or in the mountains, where, according to tradition, direct contact was established between the faithful and Saints or the Virgin Mary Herself. Manifestations occurred by means of miracles and apparitions, thereby creating a direct link between the supernatural world and believers. Religious communities, in these extraordinary places, responded to the call through the building of shrines and promotion of the cult. Over time, the faithful reached these places of mystery, performing pilgrimages with the aim of strengthening their religious faith, but also with the purpose of seeking intercession and grace. In this case, the request for clemency assumed spiritual characteristics and also became a profession of faith. Accordingly, the shrines in the Christian world are places where supernatural events may occur. In these environments the believer resorted to faith, when medicine showed its limits in a tangible way. For the above reasons, while epidemics were occurring, the requests for clemency were numerous and such petitions were both individual and collective. In particular, by means of votive offerings (ex voto) the believers, both individually and collectively, gave the evidence of the received grace to the thaumaturgical Saint. Through the votive act, a perpetual link between the believer and the Saints or Holy Virgin was forged and a strong request for communion was transmitted. The aim of the present study is to describe the role played by votive tablets (ex voto) in the last 500-600 years, as visible evidence of human suffering. From this perspective, these votive expressions may assume the role of markers because, in accordance with the expressions of popular faith, they allow us to follow the most important outbreaks that have caused distress to Christian communities.

[The Semmelweis reasoning and the puerperal fever]. / Il ragionamento di Semmelweis e la febbre puerperale.

Ignaz Philipp Semmelweis is probably one of the most important personalities of the history of medicine in nineteenth century before the microbiological Pasteur's revolution. Young doctor, troubled by the numerous deaths occurring at the obstetrician department in Wien, were he had been temporarily employed, despite the unavailability of laboratory instruments, he could get, by means of empirical observation and deductive reasoning, what all the other contemporary scientists had not been able to perceive: the responsibility of puerperae's mortality was to ascribe to genital contamination that occurred through the hands of doctors visiting them after having performed autopsies. Semmelweis is a romantic figure, who also paid for his political and cultural engagement in Wien in 1848 with social isolation. His uneasy temperament, and some difficulties in the relationship with his colleagues, didn't promote his ideas to be accepted and spread. Few years following his death, prematurely occurred in unclear circumstances, thanks to Pasteur's discoveries, his battle was eventually recognized.

[Physicians and philosophers tackling Cupid's disease: combating syphilis in the 18th century]. / Medici e filosofi alle prese con la "venere politica". II contrasto della sifilide nel settecento.

After the great fear caused by the rapid spread of syphilis in the 16th century (and the progressive contraction in the following century), the European political authorities had to tackle a disease that had become endemic. There was no solution in terms of treatment since the cause was unknown: the only precaution seemed to be the repression of such behaviour as prostitution, which seemed connected to the spread of Cupid's disease, as syphilis was called euphemistically in cultured circles. Medicine was powerless, and thinkers and philosophers helped the rulers with their ideas to develop laws to repress and reduce the incidence of the disease. In the 18th century, philosophers such as Ludovico Antonio Muratori and Peter Frank (founder of the Health Police), the priest Maria Gennaro Sarnelli, the libertine Bernard De Mandeville, the Neapolitan thinker Gaetano Filangeri, the founder of Congregazione della Carita Don Giulio Canali and the Abbot Antonio Genovesi contributed with their studies and sometimes works to focus attention on health problems in relation to syphilis prevention, even if repression remained the most widely adopted solution.

Associated actinomycosis and rhinopharyngeal adenocarcinoma during HIV infection: diagnostic and therapeutic issues.

An extremely infrequent episode of nasopharyngeal actinomycosis associated with squamous adenocarcinoma occurred in an HIV-infected male patient with a previous diagnosis of AIDS, treated with combined antiretroviral therapy taken with insufficient adherence, such that a satisfactory immune system recovery (as expressed by a CD4 lymphocyte count persistently above 400 cells/mcl), contrasted with a low-level persistence of detectable HIV viraemia, and enlarged genotypic resistance mutations. Interestingly, a number of local and specific risk factors for both infectious and neoplastic disorders were recognized by healthcare staff (tobacco smoke, long-term inhalatory substance abuse, in particular cocaine, and semi-professional mushroom-truffle hunting, including evaluation by systematic smelling). Despite appropriate and timely diagnostic assessment carried out with repeated, combined computerized tomography, magnetic resonance imaging, and fiberoptic rhinoscopy with biopsy and histopathologic studies, the final diagnosis of a combined dual infectious-neoplastic pathology occurred only after a demolishing surgical intervention and subsequent pathology studies. Despite proper antimicrobial therapy, and an associated radiotherapy and cytotoxic chemotherapy schedule, rapid dissemination of multiple secondary lesions to the brain rapidly led to our patient's death. The imaging and histopathological diagnostics of the dual illnesses of our HIV-infected patient, and its therapeutic and outcome features, are presented and discussed on the basis of the evidence from the available literature. To the best of our knowledge, this is the first described case of actinomycosis associated with a local, underlying squamous cell adenocarcinoma of the same ear, nose, and throat district in either HIV-infected or HIV-non-infected subjects.

HIV-associated early gastric adenocarcinoma successfully cured with surgery, and followed over eight years.

An extremely rare case report of HIV-associated gastric adenocarcinoma surgically treated in the year 1998 in a 37-year-old male patient already HIV positive for 10 years, with a complete post-surgery disease-free follow-up of eight years, is described. An international literature search allowed us to report the available details of the only nine cases of HIV-associated gastric cancer yet published. Seven occurred prior to the introduction of highly active antiretroviral therapy (HAART) and were burdened by a rapid disease evolution, while only two patients were reported after the introduction of HAART (like ours) and obtained surgical cure. Detailed data regarding complications, sequelae and overall survival are not given. Notably, even four of the nine published reports came from Japan, and an early disease development was usual (37-50 years of age at diagnosis). Due to its relevant differential diagnosis implications with many other HIV-related gastrointestinal disturbances caused by functional and organic diseases (drug-related disturbances, HIV infection itself, opportunistic infections, and Kaposi's sarcoma and malignant lymphomas being the most frequent disorders) and the possibility of maintaining an adequate life-expectancy when diagnosis and aggressive treatment are not delayed, gastric cancer should be considered carefully by all clinicians dealing with HIV disease.

Causes of hospitalization among extra-European Union children in a large hospital of Northern Italy, in a five-year observation period.

The hospitalizations of 1,239 patients aged 14 years or less and immigrated from extra-European Union countries in Italy were assessed in the 6-year period, from 1999 to 2004. The main demographic and clinical features were analyzed according to several variables, also distiguishing patients aged less than one year, from those aged 1-14 years. The introduction of a deed of indemnity law in 2001 profoundly changed the pattern of admissions and health care needs and exploitation during subsequent years, leading to a massive regularization of clandestine immigrants.

Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long-Term antiretroviral therapy, and with absent-negligible immunodeficiency.

A patient with HIV infection developed the first episode of AIDS-defining opportunism (severe Candida albicans esophagitis) with an underlying CD4+ lymphocyte count of 1,025 cells/microL. After treatment with a highly active antiretroviral therapy (HAART), taken with insufficient compliance and leaving a residual viral load, our patient suffered from two relapses of esophageal candidiasis, which occurred three months and seven years later, when his CD4+ lymphocyte count was 930 and 439 cells/microL, respectively, and a viral load slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida esophagitis remains one of the most common AIDS-defining diseases, but a presentation with a concurrent CD4+ count above 1,000 cells/microL remains a rare exception, as well as the two isolated, subsequent relapses, occurred with a CD4+ count ranging from 439 to 930 cells/microL, and a residual HIV viremia due to insufficient adherence to the prescribed HAART regimens. Our case report represents the opportunity to revisit the epidemiology and, especially, the pathogenesis of this opportunistic fungal complication in HIV-infected patients and in other subjects at risk, on the ground of an extensive literature review, and to explore possible alternative supporting factors other than the crude absolute CD4+ lymphocyte count, with emphasis on the possible role of a persisting HIV viremia, and other potential contributing factors. Clinicians engaged with immunocompromised patients and subjects with HIV disease, should be aware that a Candida esophagitis may occur and relapse also when the cell-mediated immunity, as measured by a simple CD4+ cell count, do not show relevant abnormalities.

[Yellow fever]. / La febbre amarilla.

After the discovery of the New World, yellow fever proved to be an important risk factor of morbidity and mortality for Caribbean populations. In the following centuries epidemic risk, expanded by sea trade and travel, progressively reached the settlements in North America and Brazil as well as the Atlantic seaboard of tropical and equatorial Africa. In the eighteenth century and the first half of the nineteenth century epidemics of yellow fever were reported in some coastal towns in the Iberian peninsula, French coast, Great Britain and Italy, where, in 1804 at Leghorn, only one epidemic was documented. Prevention and control programs against yellow fever, developed at the beginning of the twentieth century in Cuba and in Panama, were a major breakthrough in understanding definitively its aetiology and pathogenesis. Subsequently, further advances in knowledge of yellow fever epidemiology were obtained when French scientists, working in West and Central Africa, showed that monkeys were major hosts of the yellow fever virus (the wild yellow fever virus), besides man. In addition, advances in research, contributing to the development of vaccines against the yellow fever virus in the first half of the nineteenth century, are reported in this paper.

Time trends in health care needs of non-EU citizens from developing countries, admitted to a general hospital in northern Italy.

Hospitalizations of foreign patients from developing countries outside the European Union were examined for the period 1999-2004, focusing on infectious diseases and on pregnancy issues. Patients over 14 years old had 6,003 admissions, leading to 7,231 overall diagnoses. During the 6-year study period, female hospitalizations increased steadily, with a peak in 2002 (p .001). This trend was mainly due to the rise in women from Eastern Europe (p .001), which occurs at a younger mean age versus that of males (p .001). Admission of illegal immigrants, performed on an emergency basis, accounted for an average of 9.4%. This phenomenon was very frequent in 1999 (43% of admissions), but dropped sharply after 2002 (p .001), caused by changes in Italian law. The prevalent women diagnoses were ob/gyn ones: voluntary pregnancy interruption, spontaneous abortion or pregnancy complications in 30.6% of cases, and childbirths or controls of pregnancies with a favourable outcome in 18.2% of patients. These diagnoses covered nearly 50% of hospitalizations of migrant women: other admissions were due to organic, dysmetabolic, or functional disorders, while infectious diseases were less frequent (4.6%). Among men, dysmetabolic disorder and organic-degenerative diseases, or functional illnesses (36.2%), were prominent, and significantly more frequent versus women (p .001), as well as post-traumatic diseases (16.5%), and infectious illnesses (12.1%; p .001). Also generic-undefined diagnoses were proportionally numerous (6.6%): cultural-language deficiencies affected the physician-patient relationship. Among infectious diseases, the main causative organisms were Mycobacterium tuberculosis (14.9%), HIV (7.1%), HBV (3.3%), and HCV (2.6%). Upper-lower airways represented the most involved organ system (45% of discharges), followed by the gastroenteric tract (16.4%), and skin-soft tissues (7.4%), while systemic infectious diseases accounted for 14.9% of episodes. Such disorders predominated (up to 90% of cases) among non-regular migrants during 1999-2000, while after 2002 an increase in infectious disorders was observed among patients from Eastern Europe. From a health care-social perspective, although a reduced incidence of infectious diseases did not occur, the possibility of attributing them to individuals of ascertained identity and housing makes it possible to trace index patients, and ultimately strive towards well-planned and effective therapeutic-preventive interventions.