Sulfadiazine plasma concentrations in women with pregnancy-acquired compared to ocular toxoplasmosis under pyrimethamine and sulfadiazine therapy: a case-control study.

BACKGROUND: Dosing recommendations for the treatment of pregnancy-acquired toxoplasmosis are empirical and widely based on experimental data. There are no pharmacological data on pregnant women with acute Toxoplasma gondii infection under treatment with pyrimethamine (PY) and sulfadiazine (SA) and our study intends to tighten this gap. METHODS: In this retrospective case-control study, we included 89 pregnant women with primary Toxoplasma infection (PT) treated with PY (50 mg first dose, then 25 mg/day), SA (50 mg/kg of body weight/day), and folinic acid (10-15 mg per week). These were compared to a group of 17 women with acute ocular toxoplasmosis (OT) treated with an initial PY dose of 75 mg, thereafter 25 mg twice a day but on the same SA and folinic acid regimen. The exact interval between drug intake and blood sampling and co-medication had not been recorded. Plasma levels of PY and SA were determined 14 ± 4 days after treatment initiation using liquid chromatography-mass spectrometry and compared using the Mann-Whitney U test at a p < 0.05 level. RESULTS: In 23 PT patients (26%), SA levels were below 20 mg/l. Fifteen of these 23 patients (17% of all patients) in parallel presented with PY levels below 700 µg/l. Both drug concentrations differed remarkably between individuals and groups (PY: PT median 810 µg/l, 95% CI for the median [745; 917] vs. OT 1230 µg/l [780; 1890], p = 0.006; SA: PT 46.2 mg/l [39.9; 54.4] vs. OT 70.4 mg/l [52.4; 89], p = 0.015) despite an identical SA dosing scheme. CONCLUSIONS: SA plasma concentrations were found in the median 34% lower in pregnant women with PT compared to OT patients and fell below a lower reference value of 50 mg/l in a substantial portion of PT patients. The interindividual variability of plasma concentrations in combination with systematically lower drug levels and possibly a lower compliance in pregnant women may thus account for a still not yet supportable transmission risk. Systematic drug-level testing in PT under PY/SA treatment deserves to be considered.

A patient with Lyme arthritis presenting in general practice.

Lyme disease, also known as Lyme borreliosis, is caused by infection with Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) complex, a Gram-negative spirochaete bacterium. Infection in humans takes place through tick bites. In principle, Lyme disease may affect every organ of the body and may manifest in different stages. Early localised or disseminated stages are characterised by erythema migrans, lymphadenosis benigna cutis, facial palsy and arthritis and the later stages by arthritis, acrodermatitis chronica atrophicans or encephalomyelitis. The incubation time of the earlier stages varies from several days to months and that of the later stages from weeks to months or even years. Lyme arthritis commonly manifests mono- or oligoarticularly (< 5 joints). Most frequently the knee joint is affected, followed by the ankle, wrist and elbow. The work-up of Lyme arthritis should include a careful history including residence in, or time spent visiting, an endemic region, previous history of tick bite(s), and erythema migrans. In order to confirm a diagnosis of Lyme arthritis clinical findings and specific IgG antibodies are necessary. A lack of IgG antibodies practically rules out Lyme arthritis. Antibodies can be detected even years after infection(s) in asymptomatic individuals with previous Lyme disease treated with antibiotics. In general, the prognosis of Lyme disease is assumed to be good, in particular after antibiotic therapy of early manifestations.

Efficacy of rapid treatment initiation following primary Toxoplasma gondii infection during pregnancy.

BACKGROUND: Treatment of Toxoplasma gondii infection acquired during pregnancy differs in many countries. In Germany, spiramycin is given until the 16th week of pregnancy, followed by at least 4 weeks of combination therapy with pyrimethamine, sulfadiazine, and folinic acid independent of the infection stage of the fetus. If infection of the fetus is confirmed by polymerase chain reaction or if fetal ultrasound indicates severe symptoms (hydrocephalus, ventricular dilation), treatment is continued until delivery with regular monitoring of pyrimethamine and sulfadiazine concentration in maternal blood and observation of possible adverse effects. In other European countries, such as France, only spiramycin is given unless infection of the fetus is proven. METHODS: To evaluate the effectiveness of the German treatment scheme, a retrospective analysis of 685 women who showed a serological constellation consistent with primary infection in pregnancy and their children was performed. RESULTS: We found an increased transmission rate to the fetus with increased time in gestation and a decreased risk of clinical manifestations. In comparison with studies performed in other countries, the overall transmission rate (4.8%) and the rate of clinical manifestations in newborns (1.6%) were lower. CONCLUSIONS: Use of spiramycin from time of diagnosis of acute acquisition of infection by the pregnant woman until week 16, followed by pyrimethamine, sulfadiazine, and folinic acid for at least 4 weeks in combination with a standardized follow-up program is efficient in reducing transplacental transmission of the parasite and the burden of disease in the newborn.

Is serological testing a reliable tool in laboratory diagnosis of syphilis? Meta-analysis of eight external quality control surveys performed by the german infection serology proficiency testing program.

The accuracy of diagnostic tests is critical for successful control of epidemic outbreaks of syphilis. The reliability of syphilis serology in the nonspecialist laboratory has always been questioned, but actual data dealing with this issue are sparse. Here, the results of eight proficiency testing sentinel surveys for diagnostic laboratories in Germany between 2000 and 2003 were analyzed. Screening tests such as Treponema pallidum hemagglutination assay (mean accuracy, 91.4% [qualitative], 75.4% [quantitative]), Treponema pallidum particle agglutination assay (mean accuracy, 98.1% [qualitative], 82.9% [quantitative]), and enzyme-linked immunosorbent assays (ELISAs) (mean qualitative accuracy, 95%) were more reliable than Venereal Disease Research Laboratory (VDRL) testing (mean accuracy, 89.6% [qualitative], 71.1% [quantitative]), the fluorescent treponemal antibody absorption test (FTA-ABS) (mean accuracy, 88% [qualitative], 65.8% [quantitative]), and immunoblot assays (mean qualitative accuracy, 87.3%). Clearly, immunoglobulin M (IgM) tests were more difficult to manage than IgG tests. False-negative results for samples that have been unambiguously determined to be IgM and anti-lipoid antibody positive accounted for 4.7% of results in the IgM ELISA, 6.9% in the VDRL test, 18.5% in the IgM FTA-ABS, and 23.0% in the IgM immunoblot assay. For negative samples, the mean percentage of false-positive results was 4.1% in the VDRL test, 5.4% in the IgM ELISA, 0.7% in the IgM FTA-ABS, and 1.4% in the IgM immunoblot assay. On average, 18.3% of participants misclassified samples from patients with active syphilis as past infection without indicating the need for further treatment. Moreover, 10.2% of laboratories wrongly reported serological evidence for active infection in samples from patients with past syphilis or in sera from seronegative blood donors. Consequently, the continuous participation of laboratories in proficiency testing and further standardization of tests is strongly recommended to achieve better quality of syphilis serology.

Seroreactivity to and avidity for recombinant antigens in toxoplasmosis.

To improve serodiagnostic methods for the diagnosis of acute toxoplasmosis during pregnancy, a new test system has been developed and evaluated based on the use of recombinant antigens. Five recombinant Toxoplasma gondii antigens (ROP1, MAG1, SAG1, GRA7, and GRA8) were cloned in Escherichia coli, purified, and applied directly onto nitrocellulose membranes in a line assay (recomLine Toxoplasma). A panel of 102 sera from 25 pregnant women with supposed recent toxoplasmosis and from two symptomatic children was compared to a panel of 71 sera from individuals with past infection. Both panels were analyzed using a recombinant line assay for immunoglobulin G (IgG), IgM, and IgA antibodies and a reference enzyme-linked immunosorbent assay. Within the IgM-positive samples, antibodies against ROP1 were predominant regardless of the infection state. In IgG analysis a characteristic antibody pattern was found for very recent infections. This pattern changed to a different one during the time course of infection: antibodies against GRA7 and GRA8 were characteristic for very early IgG, whereas antibodies against SAG1 and MAG1 appeared significantly later. These results were further confirmed by determination of the IgG antibody avidity for every single recombinant antigen. In the time course of infection, IgG antibodies against the early recognized antigens matured significantly earlier than those directed against the later antigens did. The IgA patterns did not give reliable information about the infection time points. The data revealed that the recombinant line assay provides valuable information on the actual state of infection, especially during the early infection time points.