Osseous hydatidosis of the proximal femur: a rare diagnosis in revision total hip arthroplasty.

Musculoskeletal hydatidosis is a rare but severe disease in central Europe. This case report presents the incidental finding of an osseous hydatidosis after cementless revision total hip arthroplasty in a patient without a preoperative history of hydatidosis or any clinical symptoms. Revision total hip arthroplasty had been necessary due to a septic osteonecrosis of the femoral head 2 years after osteosynthesis of a traumatic proximal femur fracture with a sliding hip screw. The positive sample was taken out of the greater trochanter in the area of the possible former entry point for the lag screw, which was macroscopic inconspicuous. Sero-analysis could afterwards confirm the suspected diagnosis. Postoperative chemotherapy with albendazole was performed for 6 months. A full-body MRI did not reveal any further cysts. This case demonstrates a possible impact of migration on the expected pathogens in revision arthroplasty. This demonstrates that in revision arthroplasty, an infection with this parasite also has to be taken into account, if the patients come from an area endemic for hydatidosis.

[Rare retrovesical tumor manifestation of cystic echinococcosis (Echinococcus granulosus)]. / Seltene retrovesikale Tumormanifestation der zystischen Echinokokkose (Echinococcus granulosus).

Unclear pelvic retrovesical intraperitoneal tumors can be caused by cystic echinococcosis. A definitive diagnosis of this disease is highly problematic und often requires a qualified histological/parasitological assessment. It is not possible to diagnose or exclude a cystic echinococcosis purely on the basis of a serological diagnosis. A multiple organ infection can be excluded using CT diagnostics as described in this case. The Robert Koch Institute has to be notified in the case of a positive result.

[Strategies for the diagnosis and treatment of prenatal toxoplasmosis - a survey]. / Strategien zur Diagnostik und Behandlung der pränatalen.

Today, a decreasing number of infants with prenatal toxoplasmosis present with clinical signs of severe, generalised infection and cerebral involvement. The favourable clinical outcome - mild or subclinical infection - is considered to be an effect of early maternofetal treatment with spiramycin and pyrimethamine/sulfadiazine (PS). However, a Cochrane Review and a recently published European multicentre study on congenital toxoplasmosis did not only question this positive effect but also the efficiency of a postnatal long-term therapy. Both studies caused much confusion among neonatologists and paediatricians. The new setting requires an update of the diagnostic possibilities and different therapeutic strategies for prenatal toxoplasmosis. Only few prospective studies are available to compare the efficiency of different drug regimens in infected infants. However, clinical data demonstrate that the available therapeutics are not curative and cannot prevent late sequelae. Follow-up studies in pregnant women and their offspring show that prenatal parasite detection does not predict an unfavourable clinical outcome when treatment is initiated early after diagnosis. In Germany, prenatal screening is not obligatory. In case of primary maternal infection, materno-fetal therapy is recommended. A combination therapy consisting of PS is considered more effective than a spiramycin monotherapy. Treatment is recommended for all infected newborns with different strategies for infants with or without clinical symptoms. The treatment strategies of different European countries are discussed. This paper provides recommendations for the diagnosis and treatment of newborn toxoplasmosis and materno-fetal infection as well as recommendations for the clinical management of infected neonates and their follow-up, including drug monitoring.

Aspects of clinical features, diagnosis, notification and tracing back referring to Trichinella outbreaks in north Rhine-Westphalia, Germany, 1998.

52 cases of human trichinellosis were notified from 11 towns in North Rhine-Westphalia from November 1998 to March 1999. After non-typical symptoms in the enteral phase, fever, muscular ache, headache, oedema, disorder of vision and rash occurred in the parenteral phase. Trichinellosis was serologically confirmed by ELISA, IFAT or western blot. Raw sausage and minced meat produced from raw pork could be determined as probable source of infection with 44 and eight notified cases, respectively. Whereas questionable raw sausage was not available for examination, frozen minced meat from the second outbreak could be secured in households of infected people. Larvae were isolated from minced meat and were identified by PCR as Trichinella spiralis. Tracing back to the source of infection was difficult because of the long time between clinical symptoms, laboratory diagnosis and notification as well as complex trade routes for pork and its products. Trichinella cases emphasize the necessity to meet the prescribed slaughter inspection and to guarantee a reliable prove of origin for meat products especially in view of specific consumer habits, i.e. the consumption of raw meat.

Is stage conversion the initiating event for reactivation of Toxoplasma gondii in brain tissue of AIDS patients?

Reactivation of chronic toxoplasmosis resulting in Toxoplasma encephalitis (TE) is a common event in acquired immune deficiency syndrome (AIDS) patients. Conversion from Toxoplasma gondii bradyzoites to tachyzoites is a prerequisite for reactivation. Until recently, the study of stage conversion in human tissue was not possible due to the lack of antibodies that recognize stage-specific epitopes after long-term formaldehyde fixation. Using the combination of a polyclonal anti-T. gondii antibody, the cyst-stage-specific monoclonal antibody CC2, and a tachyzoite-specific polyclonal antibody (anti-SAG1, recombinant), we tried to demonstrate parasite differentiation in the brain tissue of 10 AIDS patients with clinically suspected TE. Double labeling of the stage-specific antibodies enabled us to demonstrate interconversion between tachyzoites and bradyzoites for the first time in human tissue. The study confirmed that the transformation process is nonsynchronous and that the manifestation of TE depends on the degree and site of tissue destruction caused by invading tachyzoites. The original source of tachyzoites could never be located, but a few samples suggested that tachyzoites may invade by dissemination across the blood-brain barrier. Cyst rupture as the first event in the process of reactivation was not seen. We conclude that the initial site(s) of reactivation will be destroyed by tissue-destructive tachyzoites long before clinical symptoms occur.

The past and present role of the Sabin-Feldman dye test in the serodiagnosis of toxoplasmosis.

The dye test for the detection of Toxoplasma-specific antibodies was first described by Sabin and Feldman 50 years ago. The test is highly specific and sensitive and considerable information is available on the development and persistence of dye test antibodies after primary Toxoplasma infection. However, the test uses live Toxoplasma gondii and is now only employed in a few laboratories. It is still the reference method for the serodiagnosis of toxoplasmosis, and a multicentre study comparing dye test results between different laboratories was much needed. We report in this article the results of a multicentre evaluation of the test involving nineteen laboratories in eight countries. The study revealed overall satisfactory standardization between the laboratories, but there were differences in the test protocols, the use of reference/standard preparations and the interpretation of results. There is still no agreement on the level of dye test values which reflect infection with the parasite, and conversion from titres to international units (IUs) did not improve standardization. However, the results indicated that a value of > 4 IU or a titre of 1:16 met the definition of positivity of most participants. We recommend that the dye test be retained as a reference method and that interlaboratory standardization be improved by the use of a common protocol and the expression of results in titres.

Infection and stage conversion during murine pulmonary toxoplasmosis: a study with three different strains of Toxoplasma gondii.

A murine model of pulmonary toxoplasmosis was examined morphologically and immunochemically using 3 strains of Toxoplasma gondii. BALB/c and NMRI mice were infected with tachyzoites of a virulent strain (RH) or with brain cysts of an avirulent (GAIL), or moderately virulent, strain (NED). Depending on the strain of T. gondii, the degree of infection, number of parasites, and replicative potential of T. gondii in lungs varied. In lungs of mice infected with the RH strain, the number of parasites increased in mice during the survival period. Only tachyzoites were found, as confirmed by stage-specific monoclonal antibodies. In lungs of mice infected with the GAIL strain or the NED strain, different stages of parasites were detected. Up to day 14 after infection, only tachyzoites were present, followed by bradyzoites between days 14 and 20 after infection. The number of cysts decreased and finally could not be detected in this organ. In general, the number of cysts that developed in the lungs was smaller than the number that developed in the brain.

The probability of acquiring primary Toxoplasma infection in HIV-infected patients: results of an 8-year retrospective study.

There is much hope that HIV-infected patients and AIDS patients can reckon with a prolonged survival in future. The increased survival of AIDS patients with positive Toxoplasma serology is not necessarily associated with an increased risk of developing Toxoplasma encephalitis. For HIV-infected patients with negative Toxoplasma serology, the probability of acquiring a primary Toxoplasma infection in highly endemic areas such as Germany had not been studied to date. One hundred eighty-three HIV-infected patients were followed up between 1987 and 1995 in a retrospective study. Within the cohort, 95% of the patients were male and 83% haemophiliacs. The initial (1987) and final (1995) prevalence rate of Toxoplasma antibodies was 33.3% and 36.6%, respectively. The annual rise of the primary infection rate was calculated as 0.41%. The dye test was used for the detection of Toxoplasma-specific antibodies. This assay proved to be reliable and stable during long-term observation. The rate of primary toxoplasmosis found in this long-term study was not higher than that of pregnant women in Germany. Chemoprophylactic measurements for seronegative HIV-infected patients are therefore not recommended, but regular serological screening to detect seroconverters is.

Cyst formation by Toxoplasma gondii in vivo and in brain-cell culture: a comparative morphology and immunocytochemistry study.

Formation of Toxoplasma gondii cysts was examined in cultured murine brain cells and was compared with the development of cysts in mouse-brain tissue. Cultures of mixed glial cells from neonatal mouse brain were infected with bradyzoites of the avirulent T. gondii strain DX. The development and maturation of Toxoplasma cysts was monitored for up to 63 days after inoculation. Transmission electron microscopy indicated that in-vitro-derived cysts were morphologically similar to tissue cysts and were located intracellularly, even for up to 63 days postinfection. For immunohistological and immunocytochemical examination of both in-vivo- and in-vitro-infected material, monoclonal antibody (mAb) CC2 was used. MAb CC2 was shown to detect specifically the underlying granular material of the cyst wall without binding to the limiting membrane of the parasitophorous vacuole. This reactivity of mAb CC2 allows the distinction of bradyzoite-containing cysts from parasitophorous vacuoles harboring tachyzoites both in vitro and in vivo.

Nonimmunological factors affecting the release of excreted/secreted antigens from Toxoplasma gondii cysts.

The phenomenon of released Toxoplasma gondii cyst antigens was studied immunohistochemically and cytochemically. It could be demonstrated that the preservation and localization of excreted/secreted antigens depended not only on the technique of preparation and fixation of the infected tissue but also on the preservation of the host cell. The soluble, bradyzoite-secreted amorphous cyst matrix material is released either after host cell destruction or permeabilization of the cyst wall. Ultrastructural studies could prove that the liberation of the cyst from its host cell does not affect the basic structure of the cyst wall but causes stretching of the invaginated limiting membrane.

Performance of European laboratories testing serum samples for Toxoplasma gondii.

One hundred twenty-nine European laboratories participated in a collaborative, multicentre study designed to evaluate the overall reliability of different serological techniques for diagnosis of Toxoplasma gondii infection. Five freeze-dried reference sera were distributed to each laboratory, each of which analysed the sera with its routine methods. The enzyme-linked immunosorbent assay was the technique used most frequently, followed by the immunofluorescent antibody technique. Only nine laboratories performed the Sabin-Feldman dye test. In general, there was good concordance between qualitative results, but for sera with low concentrations of Toxoplasma gondii-specific IgG antibodies, some false-negative results were found. For specific IgM and IgA antibodies, the immunosorbent agglutination assay proved the most sensitive. The present study demonstrates the need for regular assessment of laboratory serodiagnosis of Toxoplasma gondii infection.

Toxoplasma gondii antibodies in pregnant women and their newborns in Dar es Salaam, Tanzania.

The sera of 849 Tanzanian pregnant women were tested at delivery for Toxoplasma gondii antibodies with the Sabin-Feldman dye test (DT) and an immunosorbent agglutination assay. A total of 296 (35%) of these women had DT titers greater than 1:4. The percentage of women with dye test titers greater than 1:4 was 34-37% regardless of the individual ages. The rate of positivity for human immunodeficiency virus 1/2 (HIV-1/2) using Western blotting was 11.5%. There was no relationship between prevalence of a positive DT result and HIV infection nor between the intensity of the DT result and HIV infection. Sixty-four parturients had a DT titer of 1:1,000 or more. From 57 newborns of these mothers, cord sera were available and were screened by the DT and the immunosorbent agglutination assay. Seven of these were found to be positive for IgM and/or IgA antibodies. It was concluded that the rate of serologic evidence for prenatal Toxoplasma infection in cord blood samples in the present study of Tanzanian pregnant women was approximately 0.8%.

An unusual case of central nervous system cryptococcosis.

Opportunistic infections of the central nervous system (CNS) in immunocompromised patients often represent a diagnostic and therapeutic challenge due to the variety of possible infectious agents causing CNS disease. We report the case of a severely immunocompromised 43-year-old woman presenting with headache, confusion, abnormal CSF findings (cell count 237/mm3 with 50% eosinophils and elevated protein), multiple contrast enhancing lesions on CT and MRI in the basal ganglia, and serologic findings compatible with latent or reactivated toxoplasmosis with high IgA and IgG antibody titers against Toxoplasma gondii in whom a final diagnosis of CNS cryptococcosis was made. This case illustrates the considerable difficulties in the differential diagnosis of opportunistic CNS infection in the immunocompromised host. We conclude from our report that (1) the diagnosis of toxoplasma encephalitis should not be based on serological findings but rather be proven by either PCR, mouse inoculation or brain biopsy, (2) CNS cryptococcosis can be associated with marked CSF eosinophilia and multiple cryptococcomas, and (3) cryptococcomas can persist on CT and MRI despite successful antifungal treatment.