Toxoplasma gondii-specific IgG avidity testing in pregnant women.

BACKGROUND: The parasite Toxoplasma gondii can cause congenital toxoplasmosis following primary infection in a pregnant woman. It is therefore important to distinguish between recent and past infection when both T. gondii-specific IgM and IgG are detected in a single serum in pregnant women. Toxoplasma gondii-specific IgG avidity testing is an essential tool to help to date the infection. However, interpretation of its results can be complex. OBJECTIVES: To review the benefits and limitations of T. gondii-specific avidity testing in pregnant women, to help practitioners to interpret the results and adapt the patient management. SOURCES: PubMed search with the keywords avidity, toxoplasmosis and Toxoplasma gondii for articles published from 1989 to 2019. CONTENT: Toxoplasma gondii-specific IgG avidity testing remains a key tool for dating a T. gondii infection in immunocompetent pregnant women. Several commercial assays are available and display comparable performances. A high avidity result obtained on a first-trimester serum sample is indicative of a past infection, which occurred before pregnancy. To date, a low avidity result must still be considered as non-informative to date the infection, although some authors suggest that very low avidity results are highly suggestive of recent infections depending on the assay. Interpretation of low or grey zone avidity results on a first-trimester serum sample, as well as any avidity result on a second-trimester or third-trimester serum sample, is more complex and requires recourse to expert toxoplasmosis laboratories. IMPLICATIONS: Although used for about 30 years, T. gondii-specific avidity testing has scarcely evolved. The same difficulties in interpretation have persisted over the years. Some authors have proposed additional thresholds to exclude an infection of <9 months, or in contrast to confirm a recent infection. Such thresholds would be of great interest to adapt management of pregnant women and avoid unnecessary treatment; however, they need confirmation and further studies.

Clinical relevance of enteropathogen co-infections in preschool children-a population-based repeated cross-sectional study.

OBJECTIVES: This study aimed to (i) determine risk factors for enteropathogen co-infections, (ii) determine whether enteropathogen co-infections influence gastroenteritis risk, and (iii) determine whether enteropathogen co-infection occurred randomly in preschool children. METHODS: A monthly-repeated cross-sectional survey in Dutch children aged 0-48 months was conducted during October 2012 to October 2014. A total of 981 stool samples were collected along with questionnaires collecting data on gastrointestinal symptoms and potential risk factors; 822 samples were successfully tested for 19 enteropathogens using real-time multiplex PCRs. Logistic regression analysis assessed co-infections in relation to gastroenteritis and potential risk factors. RESULTS: In all, 598/822 (72.7%) stool samples tested positive for at least one enteropathogen, of which 290 (48.5%) were positive for two or more enteropathogens. Risk factors for two or more enteropathogen co-infections were young age (<12 months, OR 1.9, 95% CI 1.1-3.3; 13-36 months, OR 1.7, 95% CI 1.1-2.5, versus 37-48 months), day-care attendance (OR 1.8, 95% CI 1.3-2.5), households with three or more children versus those with one child (OR 1.7, 95% CI 1.1-2.8). Stool samples collected in spring less often had two or more enteropathogens versus summer (OR 0.4, 95% CI 0.2-0.7). Food allergy was a risk factor for three or more enteropathogen co-infections (OR 3.2, 95% CI 1.1-8.9). The frequency of co-infection was higher than expected for norovirus GI/norovirus GII, Clostridium difficile/norovirus GI, C. difficile/rotavirus, astrovirus/Dientamoeba fragilis, atypical enteropathogenic Escherichia coli/adenovirus, typical enteropathogenic E. coli/adenovirus, and enteroaggregative E. coli/astrovirus. No co-infection was associated with increased gastroenteritis risk. CONCLUSIONS: Risk factors for enteropathogen co-infections were identified and specific enteropathogens co-occurred significantly more often than expected by chance. Enteropathogen co-infections were not associated with increased gastroenteritis risk, calling into question their clinical relevance in preschool children.

The design of a Social Cost-Benefit Analysis of preventive interventions for toxoplasmosis: An example of the One Health approach.

Toxoplasma gondii infections cause a large disease burden in the Netherlands, with an estimated health loss of 1,900 Disability Adjusted Life Years and a cost-of-illness estimated at €44 million annually. Infections in humans occur via exposure to oocysts in the environment and after eating undercooked meat containing tissue cysts, leading to asymptomatic or mild symptoms, but potentially leading to the development of ocular toxoplasmosis. Infection in pregnant women can lead to stillbirth and disorders in newborns. At present, prevention is only targeted at pregnant women. Cat vaccination, freezing of meat destined for undercooked consumption and enhancing biosecurity in pig husbandries are possible interventions to prevent toxoplasmosis. As these interventions bear costs for sectors in society that differ from those profiting from the benefits, we perform a social cost-benefit analysis (SCBA). In an SCBA, costs and benefits of societal domains affected by the interventions are identified, making explicit which stakeholder pays and who benefits. Using an epidemiological model, we consider transmission of T. gondii after vaccination of all owned cats or cats at livestock farms. To identify relevant high-risk meat products that will be eaten undercooked, a quantitative microbial risk assessment model developed to attribute predicted T. gondii infections to specific meat products will be used. In addition, we evaluate serological monitoring of pigs at slaughter followed by an audit and tailor made advice for farmers in case positive results were found. The benefits will be modelled stochastically as reduction in DALYs and monetized in Euro's following reference prices for DALYs. If the balance of total costs and benefits is positive, this will lend support to implementation of these preventive interventions at the societal level. Ultimately, the SCBA will provide guidance to policy makers on the most optimal intervention measures to reduce the disease burden of T. gondii in the Netherlands.

Two cases of cutaneous leishmaniasis in Dutch military personnel treated with oral miltefosine.

INTRODUCTION: In the Netherlands, cutaneous leishmaniasis is most commonly seen in military personnel deployed on a mission or training abroad. The treatment of two Dutch soldiers who acquired cutaneous leishmaniasis with oral miltefosine was evaluated. Adverse effects were monitored and the improvement of skin lesions was assessed. CASE REPORTS: A military nurse with a painless Chiclero's ulcer due to Leishmania (Viannia) braziliensis acquired in Belize and a military physical training instructor with itchy swelling and small ulcer of the back of his left elbow due to L. donovani/infantum complex acquired in Ibiza were treated with oral miltefosine 50 mg three times a day for 28 days. DISCUSSION: Both patients responded well to oral miltefosine. Adverse effects were mild. Increase of creatinine levels was seen while liver transaminase levels were unremarkable. CONCLUSIONS: Miltefosine proved to be a convenient, effective and well-tolerated treatment option in the treatment of cutaneous leishmaniasis in Dutch military personnel.

Brachyspira species and gastroenteritis in humans.

Brachyspira species have been implicated as a potential cause of gastroenteritis in humans; this is, however, controversial. In 733 gastroenteritis cases and 464 controls, we found 29 samples positive for Brachyspira species (2.3% of cases and 2.6% of controls; P = 0.77). Brachyspira species were not associated with gastroenteritis in humans.

Simultaneous increase of Cryptosporidium infections in the Netherlands, the United Kingdom and Germany in late summer season, 2012.

Starting August 2012, an increase in Cryptosporidium infections was reported in the Netherlands, the United Kingdom and Germany. It represented a 1.8 to 4.9-fold increase compared to previous years. Most samples were C. hominis IbA10G2. A case­control study was performed in the Netherlands but did not identify an endemic source. A case­case study in the north of England found travel abroad to be the most common risk factor.

Etiology of acute gastroenteritis in children requiring hospitalization in the Netherlands.

Infectious gastroenteritis causes a considerable burden of disease worldwide. Costs due to gastroenteritis are dominated by the hospitalized cases. Effective control of gastroenteritis should be targeted at the diseases with the highest burden and costs. For that, an accurate understanding of the relative importance of the different bacterial, viral, and parasitic pathogens is needed. The objective of the present study was to determine the incidence and etiology of gastroenteritis requiring hospital admission in the Netherlands. Six hospitals enrolled patients admitted with gastroenteritis for approximately one year over the period May 2008 to November 2009. Participants provided questionnaires and a fecal sample, and the hospital filled out a clinical questionnaire. In total, 143 children hospitalized for gastroenteritis and 64 matched controls were included in the study. Overall incidence of gastroenteritis requiring hospitalization was estimated at 2.92 per 1,000 children aged 0-17 years per year, with the highest incidence in children under the age of 5 years. The full diagnostic panel of pathogens could be studied in fecal samples of 96 cases. One or more pathogens were found in 98% of these cases. Co-infections were observed relatively often (40%). Viruses were detected in 82% of the samples, with rotavirus being most common (56%), bacteria in 32% and parasites in 10%. The present study emphasizes the importance of viral pathogens, especially rotavirus, in hospitalizations of children with gastroenteritis. Policies to reduce (costs of) hospitalizations due to gastroenteritis should therefore be first targeted at rotavirus.

Aetiology of acute gastroenteritis in adults requiring hospitalization in The Netherlands.

SUMMARY Infectious gastroenteritis causes a considerable burden of disease worldwide. Effective control should be targeted at diseases with the highest burden and costs. Therefore, an accurate understanding of the relative importance of the different microorganisms is needed. The objective of this study was to determine the incidence and aetiology of gastroenteritis in adults requiring hospital admission in The Netherlands. Five hospitals enrolled patients admitted with gastroenteritis for about 1 year during the period May 2008 to November 2009. Participants completed questionnaires and provided a faecal sample. The hospital completed a clinical questionnaire. In total, 44 adults hospitalized for gastroenteritis were included in the study. The cases had serious symptoms, with 31% subsequently developing kidney failure. One or more pathogens were found in 59% of cases. Overall, rotavirus (22%) was the most common infection. Co-infections were observed relatively often (22%). This study emphasizes that rotavirus can also cause serious illness in adults.

Toxocara and Ascaris seropositivity among patients suspected of visceral and ocular larva migrans in the Netherlands: trends from 1998 to 2009.

Toxocara canis, Toxocara cati and Ascaris suum are roundworms of dogs, cats and pigs, respectively, that can also infect humans. These zoonotic helminths have a worldwide distribution and are also endemic in the Netherlands. Infection with Toxocara sp. may result in visceral larva migrans (VLM) or ocular larva migrans (OLM) caused by the migrating larvae. Although A. suum has been reported to occasionally mature to the adult stage in humans, clinical cases of VLM suspected to be caused by A. suum have been described. Diagnosis of these helminth infections relies mainly on serology. Here we analyse the results from the Toxocara and Ascaris IgG-ELISA from a total of 2,838 serum samples from VLM and OLM suspected patients that were sent to our institution from 1998 to 2009. Results indicate that for each year the Ascaris seropositivity is significantly higher compared to the Toxocara seropositivity. Furthermore, while Toxocara seropositivity has decreased over time, the Ascaris seropositivity has not significantly changed for the past 12 years. The Ascaris and Toxocara seropositivity was also shown to increases with age and, while gender has no influence on the Ascaris seropositivity, males showed higher Toxocara seropositivity.

Decreased prevalence and age-specific risk factors for Toxoplasma gondii IgG antibodies in The Netherlands between 1995/1996 and 2006/2007.

To estimate the change in the seroprevalence and risk factors for toxoplasmosis in The Netherlands, a study was conducted in the general population in 2006/2007, similarly designed as a previous study in 1995/1996. Testing 5541 sera for IgG antibodies against Toxoplasma gondii showed a marked decrease of the overall seroprevalence to 26·0% [95% confidence interval (CI) 24·0-28·0], compared to 40·5% (95% CI 37·5-43·4) in 1995/1996. In women of reproductive age the seroprevalence decreased from 35·2% (95% CI 32·9-38·6) in 1995/1996 to 18·5% (95% CI 16·2-20·7) in 2006/2007, leaving the majority of pregnant women susceptible to primary infection with T. gondii and their babies to congenital toxoplasmosis. In participants aged ≥20 years, Toxoplasma seropositivity was associated with living in the Northwest, living in urban areas, low educational level, consumption of raw pork, keeping a cat, and not having occupational contact with clients or patients. For younger participants, risk factors were keeping sheep or cattle, consumption of raw unwashed vegetables and putting sand in the mouth.

Prevalence of antibodies against Ascaris suum and its association with allergic manifestations in 4-year-old children in The Netherlands: the PIAMA birth cohort study.

The association between helminth infections and childhood atopic diseases remains controversial. The majority of studies have been carried out in tropical areas, whereas less information is available from western countries with low intensity of helminth infections. In the Netherlands, the infection of pigs with Ascaris suum is very common, particularly on pig farms with outdoor facilities. This helminth can also infect humans, causing visceral larva migrans. This study aims at determining the prevalence of antibodies against A. suum and its association with allergic symptoms and sensitisation in a population of 4-year-old children living in The Netherlands. Blood samples from 629 children from the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study were examined for Ascaris antibodies. Data on allergic symptoms and sensitisation were collected using questionnaires and radioallergosorbent tests (RAST). A total of 45 out of 629 (7%) were found to be Ascaris-seropositive. In addition, a positive association between Ascaris seropositivity and wheeze in the last year, doctor-diagnosed asthma and food and aero-allergen sensitisation was found. These results support the hypothesis that low-level or transient infection with helminths enhances allergic reactivity.

Congenital toxoplasmosis and DALYs in the Netherlands.

The calculation of disability-adjusted life years (DALYs) enables public health policy makers to compare the burden of disease of a specific disease with that of other (infectious) diseases. The incidence of a disease is important for the calculation of DALYs. To estimate the incidence of congenital toxoplasmosis (CT), a random sample of 10,008 dried blood spot filter paper cards from babies born in 2006 in the Netherlands were tested for Toxoplasma gondii-specific IgM antibodies. Eighteen samples were confirmed as positive for IgM, resulting in an observed birth incidence of CT of 1.8 cases per 1,000 live-born children in 2006 and an adjusted incidence of 2.0 cases per 1,000. This means that 388 infected children were born in 2006. The most likely burden of disease is estimated to be 2,300 DALYs (range 820-6,710 DALYs). In the previous calculations, using data from a regional study from 1987, this estimate was 620 DALYs (range 220-1,900 DALYs). The incidence of CT in the Netherlands is much higher than previously reported; it is 10 times higher than in Denmark and 20 times higher than in Ireland, based on estimates obtained using the same methods. There is no screening program in the Netherlands; most children will be born asymptomatic and therefore will not be detected or treated.

Spontaneous cure of American cutaneous leishmaniasis due to Leishmania naiffi in two Dutch infantry soldiers.

We report two Dutch infantry soldiers who acquired American cutaneous leishmaniasis (ACL) during military jungle training in Surinam. The lesions had existed for 3 and 5 months, respectively, before the soldiers presented for treatment. The lesions occurred on the head and right thigh, and were small, uncomplicated and symptomless. PCR for Leishmania revealed Leishmania naiffi in both patients. No treatment was given, and the lesions in both men healed spontaneously within 4 and 6 weeks, respectively, after presentation to our clinic. CL is one of the important 'tropical' diseases in The Netherlands, primarily due to the increasing numbers of cases in travellers and in military personnel serving overseas. ACL due to L. naiffi is thought to be a mild expression of CL with a self-limiting nature. Lesions seem to be single, mostly small, ulcerating and usually appear on the hands, arms and legs. No case of mucocutaneous leishmaniasis has yet been attributed to this parasite.

Specific IgG4 response directed against the 45-kDa glycoprotein in trichinellosis: a re-evaluation of patients 15 years after infection.

The aim of this study was to evaluate the humoral immune response in late human trichinellosis with particular attention to the presence of IgG4 antibodies directed against the Trichinella-45-kDa glycoprotein (gp). This study re-evaluates subjects 15 years after they were involved in a trichinellosis outbreak that occurred in Central Italy following the consumption of raw boar meat infected with Trichinella britovi. The results show that ELISA tests using the E/S antigen identified five IgM- and eight IgG-positive patients and no IgA-positive patients. Tests using immunoblot (IB) with E/S antigens identified three IgM-, five IgA-, seven- IgG1- and three IgG4-positive sera. When the purified 45-kDa gp was used as an antigen, the IB revealed that six of the ten sera tested were positive for IgG4. Sera were also evaluated with a commercial kit, revealing that 11 of 12 patients had a highly sensitive reactivity against Trichinella proteins (64 and 44-43 kDa). In conclusion, humoral immune response against Trichinella is still present in these patients 15 years after the initial infection, including an IgG4 response directed to the 45-kDa gp.

Disease burden of congenital toxoplasmosis.

Although the outcomes of toxoplasmosis have been well documented, an integrated estimate of the impact of this infection on the health status of the population is not available. "Disability-adjusted life years" are the sum of years of life lost and years lived with disability, weighted for the severity of the illness. The estimated disease burden of congenital toxoplasmosis in The Netherlands is 620 (range, 220-1900) disability-adjusted life years per year, which is similar to that for salmonellosis and is mainly caused by fetal loss and chorioretinitis. However, there is considerable uncertainty in this estimate. Scenario analysis indicates that the true burden may be underestimated. In other countries, the disease burden is expected to vary with the incidence of congenital infection, but it may also depend on the health care system. In countries that actively screen for toxoplasmosis, such as France, there may be a lower burden of morbidity but a higher burden of mortality.

Acute pulmonary histoplasmosis from Ghana.

A male patient developed acute pulmonary histoplasmosis 2 weeks after bathing in the water falls of Wli, Ghana. Exposure to Histoplasma capsulatum was probably mediated through inhalation of an aerosol of water and guano from the large colony of fruit bats of the falls. More cases of acute pulmonary histoplasmosis can be expected.

Genotyping of Giardia in Dutch patients and animals: a phylogenetic analysis of human and animal isolates.

Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis) is a protozoan organism that can infect the intestinal tract of many animal species including mammals. Genetic heterogeneity of G. duodenalis is well described but the zoonotic potential is still not clear. In this study, we analysed 100 Giardia DNA samples directly isolated from human stool specimens, to get more insight in the different G. duodenalis assemblages present in the Dutch human population. Results showed that these human isolates could be divided into two main Assemblages A and B within the G. duodenalis group on the basis of PCR assays specific for the Assemblages A and B and the DNA sequences of 18S ribosomal RNA and the glutamate dehydrogenase (gdh) genes. Genotyping results showed that G. duodenalis isolates originating from Dutch human patients belonged in 35% of the cases to Assemblage A (34/98) and in 65% of the cases to Assemblage B (64/98) whereas two human cases remained negative in all assays tested. In addition, we compared these human samples with animal samples from the Netherlands and human and animal samples from other countries. A phylogenetic analysis was carried out on the DNA sequences obtained from these Giardia and those available in GenBank. Using gdh DNA sequence analysis, human and animal Assemblage A and B Giardia isolates could be identified. However, phylogenetic analysis revealed different sub-clustering for human and animal isolates where host-species-specific assemblages (C, D, E, F and G) could be identified. The geographic origin of the human and animal samples was not a discriminating factor.

A one-year intensified study of outbreaks of gastroenteritis in The Netherlands.

In 2002, in The Netherlands a national study of gastroenteritis outbreaks was performed. Epidemiological information was collected by the Public Health Services (PHS) and the Food Inspection Services (FIS) using standardized questionnaires. Stool samples were collected for diagnostic testing. For foodborne outbreaks, food samples were taken. In total, 281 gastroenteritis outbreaks were included, mainly from nursing homes and homes for the elderly (57%), restaurants (11%), hospitals (9%) and day-care centres (7%). Direct person-to-person spread was the predominant transmission route in all settings (overall 78%), except for restaurant outbreaks where food was suspected in almost 90% (overall in 21% of outbreaks). The most common pathogen was norovirus (54%), followed by Salmonella spp. (4%), rotavirus group A (2%), Campylobacter spp. (1%) and only incidentally others. In conclusion, most outbreaks were reported from health and residential institutions, with norovirus as the dominant agent. Control should aim at reducing person-to-person spread. In foodborne outbreaks norovirus was common, due to contamination of food by food handlers. Salmonella, as the second foodborne pathogen, was mainly associated with raw shell eggs. These results stress the continuous need for food safety education, complementary to governmental regulation.

Population-based Toxoplasma seroprevalence study in The Netherlands.

During 1995--1996 a population-based seroprevalence study was conducted in The Netherlands. Risk factors were established for postnatally acquired toxoplasmosis. The results were compared with a study conducted during 1987-1988 in pregnant women in the Southwest of The Netherlands in order to estimate the change in seroprevalence. In total, 7521 sera were tested and the national seroprevalence was 40.5 % (95 % CI 37.5-43.4). Living in the Northwest, having professional contact with animals, living in a moderately urbanized area, being divorced or widowed, being born outside The Netherlands, frequent gardening and owning a cat were independently associated with Toxoplasma seropositivity. Risk factors like eating undercooked meat could not be studied. The seroprevalence among women aged 15-49 years was 10 % lower (35.2 %, 95 % CI 32.9-38.6) in the study of 1995-1996, compared to the Toxoplasma study of 1987--1988 (45.8 %, 95 % CI 45.2-46.3). The steepest rise in seroprevalence still occurred among the subjects aged 25-44 years.