Toxoplasma infection in individuals in central Italy: does a gender-linked risk exist?

An accurate estimate of the impact of toxoplasmosis on the population in Italy is not available. We performed a cross-sectional study on individuals living in Italy to assess: (1) differences in access to Toxo testing and in the prevalence of recent and past Toxoplasma gondii infection according to gender and age, and (2) the clinical impact of disease burden on the male patient subset. Reason for testing, condition of in- or outpatient and clinical data were analysed. Between-gender differences were observed in access to the test. Immunoglobulin M (IgM) prevalence was increased in males in the age range 5-34 years [odds ratio (OR) = 2.03, 95% confidence interval (CI) 1.18-3.49, p = 0.01), with a peak at 25-34 years. In females, it decreased in the age range 20-39 years (OR = 0.49, 95% CI 0.32-0.74, p = 0.0008). The attack rate of recent infection was twice as high for males than for females. Estimates pointed out 3.3 and 1.7 events in 1000 at-risk person-years in the male and female cohorts, respectively. Most IgM-positive subjects did not experience severe forms of toxoplasmosis, with 35% having lymphadenopathy. Chorioretinitis, systemic and neurological manifestations were also observed. Our findings suggest that the acute phase of toxoplasmosis is largely unapparent or clinically mild in this area. It is also possible that the disease burden for Toxoplasma infection in Italy is underestimated. Further study should focus on information acquisition and Toxo test access in hospital units for a better estimation of the real burden of mild and severe forms of the disease.

[Update for the standard procedures of diagnosis and therapy in cases of congenital rubella]. / Aggiornamento delle procedure operative standard per la diagnosi e la cura dei casi di rosolia congenita.

Congenital Rubella is the dramatic consequence of rubella during gestation. A combined strategy of Measles and Rubella universal vaccination on children and selective vaccination of susceptible women has been shown effective in the elimination of congenital rubella requiring an incidence of < 1 case of CRS per 100,000 live births. Verification processes of rubella elimination require that physicians early and appropriately diagnose all cases of congenital rubella, including those unpatent at birth. The paper highlights clinical and laboratory aspects channeling diagnosis of congenital rubella infection or syndrome even after the first year of life, and the short- and long-term management criteria.

Seroprevalence for toxoplasmosis in individuals living in north west Tuscany: access to Toxo-test in central Italy.

This survey aimed to estimate the prevalence of anti-Toxoplasma IgG and IgM antibodies in people living in north west Tuscany (central Italy) and to investigate the adherence to antenatal screening programs and access to the Toxo-test as well. Sera from a large sample of individuals suspected to have acute infection or from pregnant women (10,352 subjects) aged between 1 day and over 70 years were analysed for both IgG and IgM anti-Toxoplasma antibodies using an immunoenzymatic method or a chemo-luminescent immunoassay. Overall, the seroprevalence of IgG antibodies was 21.4% (95% CI 20.62-22.20). A positive trend according to age was found, with low positivity observed in younger age groups. Among women of reproductive age the prevalence of IgG antibodies was 19.4% (95% CI 18.64-20.26). The overall IgM seroprevalence was 1.07% (95% CI 0.87-1.27). A low IgM prevalence was also observed in women of reproductive age (0.8%; 95% CI 0.65-1.03). Our study seems to indicate that primary prevention is widespread among women. However, an epidemiological surveillance system for toxoplasmosis should be implemented, to assess the risk of congenital toxoplasmosis and to determine the true burden of disease in adults.

Prenatal diagnosis of congenital rubella infection and ultrasonography: a preliminary study.

AIM: The aim of this study was to analyze the role of ultrasonography in the prenatal diagnosis of women with confirmed rubella infection in pregnancy. METHODS: We performed a retrospective, population-based study on 175 women referred to our Centre of Infectious Disease in Pregnancy of AOU Federico II for rubella infection, in the period between January 1999 and December 2009. In confirmed cases of infection we performed periodic ultrasonographic assessment of fetal anatomy looking for prenatal findings of rubeovirus infection. Neonatal outcomes were collected. RESULTS: Among 175 women, 48 (27.4%) were confirmed cases, in 83 (47.4%) cases rubella infection remain suspected. The remaining 44 (25.1%) women were excluded to having rubella infection in pregnancy. No defined probable cases were found. Among children born to mother with confirmed rubella infection, 9 (18.7%) resulted infected by rubella virus. In particular 6 newborns (66% of the affected) were asymptomatic, two babies showed incomplete congenital rubella syndrome (CRS), due to the presence of deafness in the absence of other congenital abnormalities without showing any USG findings. Only one baby showed a complete CRS: USG prenatal rubella infection findings were IUGR, polydramnios, cardiomegaly, defects of atrial septum, hepatosplenomegaly, ascites, echogenic bowel, placentomegaly. USG specificity and sensitivity was 100% and 11% respectively. CONCLUSION: USG has an important role in the detection rubella intrauterine infection in case of severe abnormalities. The obstetricians should understand the limitations of ultrasound in detection of deafness and minor abnormalities.

Risk factors for toxoplasmosis in pigs bred in Sicily, Southern Italy.

The aim of the study was to determine the seroprevalence of Toxoplasma gondii infection in pigs raised and slaughtered in Sicily, Southern Italy, and to evaluate the risk factors associated with the infection. Samples were collected in seven slaughterhouses and on-site on 274 raising farms across Sicily, in the period from January 2006 until March 2007. For each sampled pig born and raised in Sicily, information was obtained on gender, age, origin, final destination of meat and farm management. Data on the farm included: farming type, presence of cats and dogs, rodent control by rodenticides, cleaning methods, water supply, altitude and herd size.T. gondii-specific antibodies were detected using a commercial Enzyme-Linked Immunosorbent Assay (Institut Pourquier, France).Antibodies against T. gondii were found in 16.3% of Sicilian pigs. The lowest seroprevalence, 7%, was found in the age group 5-7 months (market pig) and the highest, 19%, in the age group >24 months. Risk factors for seropositivity were: age 11-24 months compared to younger (OR 5.62; CI 1.52-20.8); farrow-to-finish farming type (OR 6.85; CI 1.87-25.01) compared to finishing and farrow-to-breed type; less than 50 pigs on the farm (OR 6.8; CI 1.76-26.2); no use of rodenticides (OR 2.71; CI 1.10-6.64), use of water coming from private sources (especially wells; OR 2.8; CI 1.03-7.72).Pigs raised in Sicily shows a high prevalence of antibodies against T. gondii. Pre-harvesting interventions to lower the risk of locally produced meat consumption for consumers should point as soon as possible to increase hygienic condition on the farm, by carefully removing waste with automatic cleaning and reducing biohazard by rodent control. Consumers must receive information on the correct handling and cooking locally produced pork meat derivatives.

Prenatal screening for congenital toxoplasmosis in Campania: preliminary report on activities and results.

By 1997, an open cohort of 1,652 live newborn of 1,637 mothers with gestational toxoplasmosis had been recruited in the Campania region to monitor the burden of congenital toxoplasmosis (CT). Of the 1,556 mother-child pairs that completed the follow up, 92 definite cases were detected, yielding a 5.9% (4.8-7.1 95% CI) transmission rate. The onset was patent for 43% of patients and sensorineural complications were shown for a further 15% of subclinical onset patients later than two years of age. The overall prevalence of toxoplasmosis during gestation was 2.46 of 1,000 deliveries, while the prevalence of definite CT was 1.38 of 10,000 live newborns. However, there is still room for intervention, as only 23% of the maternal diagnoses were proven through seroconversion, 63 of the late-gestation seroconverters remained untreated, and six probable CT diagnoses were made following referrals due to patent sequelae and born during the study period. There was a positive secular trend on the rates of infant referral and definite CT diagnosis, according to the live birth rate (Chi2 for trend < 0.001). Extension of this surveillance system across the country could help to define a future strategy for prevention.

Congenital toxoplasmosis: the state of the art.

A century after the first description the best preventative strategy against CT is still matter of debate. Over Europe, where prenatal and newborn screening are overspread, effectiveness/cost ratio remains undemonstrated.

Toxoplasma gondii infections in sheep in Sicily, southern Italy.

The aim of the study was to determine the burden of Toxoplasma gondii-infections in sheep in Sicily, southern Italy and the risk factors for infection. Sera from 1961 sheep were collected just before slaughtering from 62 farms located in 8 out of 9 Sicilian administrative districts. The sera were analysed for Toxoplasma-specific IgG antibodies using commercially available enzyme-linked immunosorbent assay. Sheep less than 4 weeks old were further analysed by ELISA for Toxoplasma-specific IgM-antibodies. Data on farm size and location were obtained from slaughterhouse sanitary reports and through structured telephone interviews of the veterinary officers from public health districts. The overall seroprevalence of Toxoplasma-specific IgG-antibodies were 49.9% (937/1876) by ELISA. Eighty-seven (54/62) percent of the farms had at least one Toxoplasma-positive animal. All the farms fed the animals outdoor on pasture and only one was claiming organic farming. Having cats on the farm, age of the animals, farm size and the use of surface water sources for drinking were all significantly associated with T. gondii-infected animals on the farm. T. gondii infection in mutton used for human consumption is very prevalent, and eating unprocessed sheep and lamb meat has a high risk of transmitting infections to humans. The presence of cats on the farm, farm size and using surface water as drinking water for the animals were risk factors for infection in sheep, with age as a significant confounder.

Sensorineural Hearing Loss in a Patient Affected by Congenital Cytomegalovirus Infection: Is It Useful to Identify Comorbid Pathologies?

Sensorineural hearing loss (SNHL) is a common defect with a multifactorial etiology. Congenital cytomegalovirus infection (cCMV) is the most common infectious cause, and its early detection allows a prompt pharmacological treatment that can improve hearing prognosis. In a consistent percentage of profound SNHL, genetic causes and/or inner ear malformations are involved; their prompt diagnosis might change therapeutic options. This study reports a case of a 3- year-old female patient with symptomatic cCMV infection who also exhibits developmental delay, dysmorphic facial features, bilateral hearing loss, and cochlear incomplete partition, type 2, in 7q21.3 deletion. This deletion includes the genes DLX5 and DLX6 , which could be the candidate genes for the ear malformation named incomplete partition, type 2.

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.

BACKGROUND: We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres. METHODS: Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks. RESULTS: The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres. CONCLUSION: Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies.

Identification of a human immunodominant B-cell epitope within the GRA1 antigen of Toxoplasma gondii by phage display of cDNA libraries.

Excreted secreted antigens of the protozoan parasite Toxoplasma gondii play a key role in stimulating the host immune system during acute and chronic infection. With the aim of identifying the immunodominant epitopes of T. gondii antigens involved in the human B-cell response against the parasite, we employed a novel immunological approach. A library of cDNA fragments from T. gondii tachyzoites was displayed as fusion proteins to the amino-terminus of lambda bacteriophage capsid protein D. The lambda D-tachyzoite library was then affinity-selected by using a panel of sera of pregnant women, all infected with the parasite. Some of the clones identified through this procedure matched the sequence of the dense granule GRA1 protein (p24), allowing us to identify its antigenic regions. In particular, the analysis of human antibody response against the recombinant GRA1 antigen fragments revealed the existence of an immunodominant epitope (epi-24 peptide).

Rubella control in Italy.

In Italy, rubella vaccination has been recommended since 1972 for pre-adolescent girls, and since the early 1990s for all children in the second year of life. Nevertheless, coverage in children from 12 to 24 months of age is suboptimal (i.e., 56% in 1998, 78% in 2003), with wide variations among regions. As a result, rubella is still circulating in Italy, and in 1996 the percentage of women susceptible to rubella between 15 and 39 years of age was >5%. Congenital rubella syndrome (CRS) was a notifiable disease between 1987 and 1991, with a range of 8-76 cases reported annually. Since 1992, national incidence data are no longer available, but local reports show that CRS cases are still occurring. Nationwide, coordinated and uniform actions are needed to control CRS effectively. For this reason, the National Plan for the Elimination of Measles and of Congenital Rubella has recently been launched. This plan includes strategies aimed at increasing MMR vaccination coverage in children and specific control measures for congenital rubella control, i.e., improving the vaccination of susceptible women of childbearing age, and reintroducing national surveillance of CRS.

Rubella control in Italy.

In Italy, rubella vaccination has been recommended since 1972 for pre-adolescent girls, and since the early 1990s for all children in the second year of life. Nevertheless, coverage in children from 12 to 24 months of age is suboptimal (i.e., 56% in 1998, 78% in 2003), with wide variations among regions. As a result, rubella is still circulating in Italy, and in 1996 the percentage of women susceptible to rubella between 15 and 39 years of age was >5%. Congenital rubella syndrome (CRS) was a notifiable disease between 1987 and 1991, with a range of 8-76 cases reported annually. Since 1992, national incidence data are no longer available, but local reports show that CRS cases are still occurring. Nationwide, coordinated and uniform actions are needed to control CRS effectively. For this reason, the National Plan for the Elimination of Measles and of Congenital Rubella has recently been launched. This plan includes strategies aimed at increasing MMR vaccination coverage in children and specific control measures for congenital rubella control, i.e., improving the vaccination of susceptible women of childbearing age, and reintroducing national surveillance of CRS.

[Control of congenital toxoplasmosis in Italy: The project of the Istituto Superiore di Sanità]. / Il controllo della toxoplasmosi congenita in Italia: il progetto dell'Istituto Superiore di Sanità.

Toxoplasma gondii infection during pregnancy is a public health concern; many resources are used in diagnostic and therapeutic activities, sometime with a low benefit/cost due to lack of standardization in practices. In the lack of suitable epidemiological knowledge at national level regarding the congenital toxoplasmosis trend in Italy, an evaluation of the public health impact of this pathology is required. The Istituto Superiore di Sanità (ISS) has worked out a project on a prevalence-incidence study at national level, performing standard reference methods for diagnosis and both case definition and case management. Furthermore, the ISS urges all the involved centers on congenital toxoplasmosis to set up a network for an active collaboration to this project.

Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis.

OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.

[Juvenile chronic arthritis]. / L'artrite cronica giovanile.

Juvenile chronic arthritis is the most common connective tissue disease in children. It is of great social and clinical interest for its chronicity, for the often unpredictable response to pharmacological treatment; for the spontaneous evolution toward infirmity and often blindness. The English classification of the disease is here been adopted. There are 3 different types of onset: systemic, poliarticular and pauciarticular. Large joints such as the knees, wrists and ankles are involved more often than small joints. Also the cervical spine is frequently affected. Systemic disease is accompanied by high spiking fever, rash, lynphoadenopathy, pericarditis and hepatosplenomegaly. Chronic uveitis is a feature of JCA, more frequently observed in pauciarticular than in the other types of onset, and it is almost always associated with antinuclear antibody seropositivity. Rheumatoid factor (RF) and subcutaneous nodules are unusual in JCA. Diagnosis is often not easy and it is essentially clinical. The diagnostic criteria adopted have been proposed by ARA in 1977. In the majority of children treatment with ASA is successful. Sometimes other types of more toxic drugs such as gold salts or penicillamine are needed. Their use is best confined to reference centers. Orthopedical and physiotherapic treatments are complementary to the pharmacological one. Multidisciplinary centers are therefore necessary for the total management of these children also to stress the importance of furthering physical and psychological growth.

What do we know about risk factors for infection in humans with Toxoplasma gondii and how can we prevent infections?

Fourteen case-control studies evaluating the importance of different risk factors for infection of humans with Toxoplasma gondii were identified. Surprisingly, up to two-thirds of infections could not be explained by risk factors such as consuming raw or undercooked meat or poor kitchen hygiene. Few studies reported population attributable risk, and when reported, it was low. Protocols including questionnaires used for collecting data, age and socio-economic groups studied, and sample sizes varied among studies. There is a need for carefully planned, case-control studies to identify sources of infection with T. gondii in humans. New risk factors, such as the manufacture of organic meat, and possible ways to sterilize meat to inactivate T. gondii tissue cysts are discussed.