[Human cystic hydatidosis in Italy: a public health emergency? Past to present]. / Idatidosi cistica umana in Italia: un problema di salute pubblica? Passato e presente.

Starting from 1991 the Central Office of Statistics ISTAT, according to changed regulations on notification of infective diseases, stopped reporting official national data on human hydatidosis. On the other hand until then notified data, concerning only about a hundred cases per year in mean during the last decades and just 36 in 1991, appeared unreliable, suggesting a diffusion far from the actual. Owing to specific studies on different research groups it is possible to try to describe a not exhaustive but indicative pattern of trend of human hydatidosis in Italy. More recent publications regarding different regions report an annual mean incidence rate of surgical cases of 9.77/100,000 inhabitants in Sardinia, of 1.57 in Emilia Romagna, of 2.30 in Sicily and of 2.33 in Apulia, the latter encompassing only hepatic cysts treated in the region, irrespective of residence of subjects. A comparison with previous studies regarding the period between 1948-1952 and 1980-84 respectively, indicates an increase in the more recent surveys. However, as even underlined by Authors, former surveys were not all-embracing (for example not including patients from private Clinics etc). On the other hand during time, improvements in surgical as well in anaesthesiological skills have made surgery possible in patients previously inoperable, and particularly in old subjects. Conversely, at present, availability of alternative therapies such as chemotherapy, PAIR or modified PAIR-based techniques may allow cases to avoide surgical surveys. However, actual parasite burden in humans may be estimated by assessing the trend of likely young cysts, as due to recent infections. Rate of pulmonary cysts, that are sure to be young, was of 48.6%/100,000 inhab. in 1952 in Italy, then falling to 18.2 in 1980-84 in the 9 considered regions, to 12.7 in Sicily (1989-91), 6.5 in Emilia-Romagna (1989-93) and 15.7 in Sardinia (1990-95). Another "class" of surely young cysts regards all cysts in young age group that necessarily have been recently infected. Ratio of infection rates in the old/young people was around 1 in 1941-52 but was exceeding 3 in 1980-84. In addition available data from more recent surveys indicate that ratio is at present still relatively low in Sardinia (3.9), where sheep-breeding is widespread, and dog-livestock-man interaction is most likely to exist, and conversely is very high in Emilia-Romagna (5.75) where pastoral economy is not prevalent (just 92,000 sheep). Actual trend both parasitological and in terms of public health would ameliorate if studies were provided with long temporary series. In Sardinia all hydatid cases surgically treated from 1969 to 1995 have been registered and analysed with a standardized methodology. During the considered period incidence appears nearly unvaried (16.9 in 1969 vs 15.8 in 1985), with a fall only for the last 5 years (9.1 in 1995), and with an increase regarding 1984-88 period. Analysis according to cyst localization strongly suggests that fall in the last period is only weakly related to hepatic cysts, that conversely are near completely responsible of rise in 1984-88. On the contrary for pulmonary cysts, i.e. young cysts, a slow but continuous and significant decrease (from 6.5 in 1969 to 1.4 in 1995) is evident. In the same way the above- mentioned old/young ratio rises from 1.7 (1969-79) to 3.9 (1990-95). On the whole analysed data suggest that although parasitic burden, strong in central-south Italy for decades, is now slow lowering due to structural changes and improvements in general conditions of life rather to specific preventive actions, human hydatidosis still represents a public health problem that will continue in the future as, because of latency, incidence rates will stay long relevant.

Causality or coincidence: may the slow disappearance of helminths be responsible for the imbalances in immune control mechanisms?

Intestinal infection continues to be a problem worldwide and helminths, which currently infect billions of individuals, are primary culprits. The major burden of disease falls on the populations of developing countries, given that over the last four to five decades helminth infections are disappearing in industrialized societies. In developing countries, a major source of immunomodulatory signals in post-natal life are parasites, particularly helminths, which, unlike most bacteria and viruses, selectively stimulate Th2 function. Helminths and their eggs are probably the most potent stimulators of mucosal Th2 responses. Responses elicited by worms can modulate immune reactions to other parasites, bacterial, viral infections and several unrelated diseases. Bacterial and protozoal infections may also protect against atopy and asthma, through the induction of the Th1 regulatory responses. Today, people in developed countries often live in ultra-hygienic environments, avoiding exposure to viruses, bacteria, ectoparasites and endoparasites, particularly helminths. Perhaps failure to acquire worms and experience mucosal Th2 conditioning predisposes to unrelated diseases. In contrast to this hypothesis it has also been suggested that Th2 responses can make the host more susceptible to other important diseases and to contribute to the spread of them.

Study on immunobiology in endoparasites of public health interest: echinococcosis-hydatidosis.

Cystic echinococcosis caused by Echinococcus granulosus is one of the most widespread zoonoses in the Mediterranean, endemic in some regions such as Sardinia. Some aspects of the research conducted in this area are briefly reviewed for an integrated analysis of both epidemiological and immunobiological knowledge, gained from field observations and experimental studies. Data on epidemiology in intermediate hosts, immunological assessment of exposure in humans, immune response and Th1/Th2 polarization in secondary experimental hydatidosis, kinetics of response in definitive host and cytokine production in experimental models are briefly reported. They confirm the usefulness of an immunobiological approach both in intermediate and definitive hosts and their potential in prevention, monitoring and control of E/H.

Study on immunobiology in ectoparasites of public health interest: Rhipicephalus sanguineus.

The recently defined range of Mediterranean Spotted Fever (MSF) in Sardinia coincides with that of the widely studied Rickettsia conorii vector, the brown dog tick Rhipicephalus sanguineus. This tick is major vector of disease in humans, domestic and wild animals. Characteristic features of the vector with respect to their seasonal activity, abundance as well as incidence of human-tick contact and how these factors influence the incidence of MSF were studied. This paper also looks at host, pathogen and tick vector interactions, re-examining some of the immunobiological parameters involved. However, the primary objective of this research is to develop a strategy that will allow better and safer tick control.

Epidemiology of hydatid disease in the Mediterranean basin with special reference to Italy.

Hydatidosis, caused by dog tapeworms of the genus Echinococcus, is one of the most important cestode infections in man. Of the four species of the genus Echinococcus, only Echinococcus granulosus is widespread in the Mediterranean basin which is still, unfortunately, a major endemic focus. This article critically reviews its diffusion in humans and sheep over the past twenty years. Although most of the available data are scarce, fragmentary, and not homogeneous, they represent the only possibility at present of evaluating the parasitic pressure.

Long-term health effects of the occupational exposure to DDT. A preliminary report.

We conducted a proportional mortality study of 1043 deaths among men who took part in an antimalarial campaign in Sardinia, Italy from 1946 to 1950. DDT comprised 94% of the insecticide used during the campaign, and was sprayed over the soil of the entire region at an average concentration of 10 mg/m2, as well as in all dwellings and animal shelters. Expected deaths were derived from the proportional mortality rates of the general Italian male population, specific by cause, 5-year age groups, and 5-year calendar periods in the period from 1956 to 1992. The proportional mortality ratio (PMR) for cardiovascular diseases was significantly decreased, while nonmalignant respiratory diseases showed a 22% increase in risk of borderline statistical significance. Significant increases in risk among workers exposed to DDT in application or inspection jobs were observed for liver and biliary tract cancer (PMR = 228; 95% C.I. = 143-345) and multiple myeloma (PMR = 341; 95% C.I. = 110-795). The PMR for myeloid leukemia was also increased (PMR = 189; 95% C.I. = 38-552), although it was not statistically significant. PMRs for liver and biliary tract cancer and myeloid leukemia were also elevated among workers who did not have direct occupational contact with DDT (liver and biliary cancer: PMR = 210; 95% C.I. = 117-346; myeloid leukemia: PMR = 170; 95% C.I. = 19-614). No trends occurred according to length of employment in exposed jobs. These preliminary results are somewhat in agreement with experimental studies in rodents and previous epidemiologic findings. Expansion of the cohort to include all applications, and collection of information to improve exposure assessment is needed to clarify these findings.

Hydatidosis: a comprehensive view of the Sardinian case.

In Sardinia the close association of sheep, dogs and humans still exists in some parts of the region, so that ideal conditions persist for the perpetuation of the parasite's life cycle. Two factors contribute to the spread of the disease: the practice of slaughtering sheep at home and the proliferation of dogs, mainly strays. This paper reviews the epidemiological picture and the economic consequences of the disease in man and livestock, strongly suggesting that this endemic disease is a major public health problem.

Immune stimulation and Hymenolepis nana cysticercoid expulsion in C3H/He and BALB/c mice.

Adoptive transfer of immunity with heterologous and homologous immune serum, and drug-abbreviated immunizations were used in C3H and BALB/c mice to determine the strain-characteristic time of expulsion of H. nana cysts. Transfer of immune serum did not accelerate worm expulsion in C3H, while elimination of worms was virtually complete by day 8 in BALB/c mice. Loss of worms was also obtained when BALB/c mice were stimulated with abbreviated infections using 20 or 1000 H. nana eggs. The immunizing infection terminated immediately after the tissue phase. After similar immunizations C3H mice again appeared slow responders but were able to affect the intestinal worms population after the higher immunizing infection. The data obtained suggest that the time of worm expulsion was related to the genetically-determined ability of the mice to respond and was independent of the stimulations used for immunization. A quantitative difference in response is proposed to explain the slow responder status of C3H.

Specific cross-immunity between Hymenolepis nana and H. diminuta: effects of transfer of immunity with homologous and heterologous immune mesenteric lymph node cells in BALB/c mice.

In BALB/c mice, Hymenolepis nana and H. diminuta stimulate a strong response. Accelerated expulsion of adult worms, as well as protection against larvae, occurred anamnestically when homologous or heterologous mesenteric lymph node cells from immune mice were transferred before challenge. The results further support the hypothesis that worm expulsion is a thymus dependent phenomenon. The extensive cross reactivity found is discussed in relation to the distinctive characteristics of the two worms. These results strongly suggest that there are antigenic similarities between the two parasites and that the accelerated expulsion of heterologous challenge infections is the result of a specific response to shared antigens.

Failure to demonstrate suppressor T cell activity in the lamina propria of Hymenolepis diminuta-infected rats.

The aim of this study was to examine whether there was an increase of suppressor T cells, relative to helper T cells, in the intestinal lamina propria of Hymenolepis diminuta-infected rats, a condition which might allow the parasite to survive for the life-span of the host. Lamina propria cells were isolated by enzymatic procedure. All lymphocytes were passed over nylon wool columns in order to remove B cells; then the T cells were purified by a panning technique using monoclonal anti-T cell antibodies. Changes in the mitogen-stimulated synthesis of IgM, IgG and IgA by normal peripheral blood indicator lymphocytes, as measured by sandwich ELISA, was used as an index of help and/or suppression. No significant suppressor T cell activity was observed in the cultures, either from control or infected intestine.

[Epidemiology and social/health implications of hydatidosis in Sardinia]. / Epidemiologia ed implicazioni socio-sanitarie dell'idatidosi in Sardegna.

All surgically treated cases of hydatidosis registered in Sardinia from 1969 to 1984 have been analysed. The 16-year period clearly shows that unilocular hydatid disease caused by larvae of tapeworm, Echinococcus granulosus, is endemic in Sardinia. In this region there are foci of human infection notably in the sheep rearing areas, of Nuoro and Sassari. The incidence of human hydatidosis shows a marked regional variation varying during the last survey (1982-1984) between 16.9/1000 in the province of Nuoro to 8.3/1000 in the province of Cagliari. Not all population is at equal risk e.g. 47.1/1000 is the incidence in shepherds respect to 8.9/1000 in employed in services. In Sardinia, although there are a wide variety of suitable intermediate host species, is sheep the determinant host for the perpetuation of the parasite's life cycle. The prevalence rate in cattle, pigs and goats in under 30% while the sheep incidence is extraordinarily high, over 90% are infected. The dogs showed a prevalence rate of 10-20%, the infection was more frequent in shepherd-dogs and strays. The rate of hydatidosis in man appears significantly correlated with number of dogs and sheep per inhabitants. Two factors are, at present, determinant in the dissemination of hydatidosis: the common sardinian practice of slaughtering sheep at home and the indiscriminate proliferation of dogs which mainly live as strays. The epidemiological picture and the economic consequences of hydatidosis in man and livestock, a damage of 28 billions of liras per year, strongly suggest this disease as a major public health problem in Sardinia.

Adoptive transfer of immunity with peritoneal exudate cells to the cestode Hymenolepis nana.

Under certain conditions, peritoneal exudate cells (PEC) removed from Hymenolepis nana-eggs infected mice, transferred to normal recipients severely inhibited the establishment of worms from a challenge infection, as expected in an immune state. A close relationship was observed between numbers of challenge worms and immune response. A significant effect was clearly demonstrable when the highest dose of eggs (150) was used, but the effect was less and not significant different when a smaller doses (30) was administered.

Blast cell activity in mice infected with Hymenolepis nana, H. diminuta and Trichinella spiralis: in vivo uptake of 125IUdR in lymphoid tissues and gut.

The kinetics of the lymphoblast response in mice during the course of a primary infection with Hymenolepis nana was measured by the in vivo uptake of 125IUdR. The response was most marked in tissues local to the site of infection, involving the nodes draining the small intestine but not other areas, e.g., inguinal lymph nodes. A close correlation between these responses and the course of infection was observed. Uptake of 125IUdR was greatest in the mesenteric lymph node (MLN) but the peak reached in this organ was later than that in Peyer's patches (PP), small intestine (SI) and spleen (S). The increase in lymphoblast activity of the MLN was similar with Trichinella spiralis; no significant blast cell response to infection with H. diminuta was found till day 9 after injection, the results being similar to those obtained when H. nana infections were established using cysticercoids rather than eggs. It has been shown that the increase in lymphoblast activity was closely correlated with the presence of cells which are most effective in adoptive transfer immunity. A dose-dependent effect was detected in blast cell activity of MLN in different infection levels with T. spiralis and H. nana.

Vaccination against the gastrointestinal helminths Trichinella spiralis and Hymenolepis nana: relationship between routes of immunization and effective protection.

Mice immunized with antigens derived from Trichinella spiralis muscle larvae or Hymenolepis nana embryos were found to be protected against the homologous challenge infection. Intraperitoneal route was found the most effective in stimulating protection compared with subcutaneous or intravenous administration. Even a single dose of antigen administered intraperitoneally stimulated a significant protection. The results of our experiments confirm that the route of administration has a noteworthy influence on the effectiveness of the immunization. The possible mechanism involved in rejection of both worms population are discussed.