Waldenström's macroglobulinemia - clinical symptoms and review of therapy yesterday, today and tomorrow.

BACKGROUND: Waldenström macroglobulinemia (WM) is a lymphoplasmocytic lymphoma with immunoglobulin M monoclonal protein. The incidence of this disease is very low (0.4/100,000), so that this disease can be regarded as an orphan's disease. It means that new drugs are often tested and registered for more frequent diseases. PURPOSE: In this review we will focus on the efficacy of the new drugs for WM. RESULTS: The current treatment options for symptomatic WM patients include alkylating agent cyclophosphamide and anti-CD20 monoclonal antibodies. Therapy with rituximab and bendamustin resulted in longer therapeutic response then therapy with rituximab, cyclophosphamide and dexamethasone. Many drugs, used in multiple myeloma (MM), shoved promising results in WM patients. Bortezomib is effective in WM, but its neurotoxicity is higher in WM than in MM patients. Therefore, new proteasome inhibitors, carfilzomib and ixazomib, are better tolerated as documented in several studies. New types of antiCD20 antibody (obinutuzumab) can be used in patients with rituximab intolerance. in five of our patients with WM, obinutuzumab and bendamustin reached deeper responses than therapies administered in previous lines of therapy. Oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab have extended the treatment options for WM patients. New BTK inhibitors (e. g. acalabrutinib, zanubrutinib, and vecabrutinib) were tested and their lower toxicity (atrial fibrillation) was documented. Moreover, the BCL2 inhibitor venetoclax is newly tested. CONCLUSION: New antiCD20 antibody (obinutuzumab) is of advantage in patients with WM with rituximab intolerance as well as bendamustin and new proteasome inhibitors (ixazomib and carfilzomib) or new BTK inhibitors with lower cardiotoxicity. Many of the abovementioned drugs do not have official registration for WM and can be administrated with the consent of the health care provider only. Thus, this work brings evidence of their efficacy.

Ixazomib - lenalidomide - dexamethason in heavily pretreated multiple myeloma patients - case reports.

BACKGROUND: The treatment of aggressive multiple myeloma (MM) patients, resistant to several treatment modalities, is very difficult in the real-world-evidence conditions. Ixazomib is a second-generation oral proteasome inhibitor. In combination with lenalidomide and dexamethasone, it is an effective and low-toxic treatment regimen for patients with relapsed or refractory MM. OBSERVATION: The presented case reports of two patients with an aggressive course of MM demonstrate the surprising effectiveness of this regimen. CONCLUSION: Repeated treatment with a combination of proteasome inhibitors (ixazomib) and immunomodulatory drugs (lenalidomide) may lead to significant clinical benefit in some patients and should be considered even in end-stage disease patients.

High "fitness age" as a risk factor for morbidity and premature mortality.

The level of cardiorespiratory capacity, as measured by maximum VO(2)max oxygen consumption, is a significant factor related to the risk of metabolic syndrome, coronary heart disease and other health disorders. A total cohort of 2901 examinations was divided into 5 groups according to the nature of physical activity: group A - endurance athletes, group B - team sports players, group C - other competitive athletes, group D - recreational leisure-time athletes, group E - people with health problems. Cardiorespiratory fitness was assessed according to the VO(2)max and METmax parameters found in the stress test on a bicycle ergometer. A gradually increased load until exhaustion was used. While in groups A to D cases that would be classified as NYHA 1 (METmax lower than 9) were quite rare (10 cases out of 2777, i.e. 0.3 %), in groups E it was 20 % in men (16 cases out of 82) and 52 % in women (23 cases out of 44) of those examined. Accordingly, fitness age in groups A, B and C generally corresponded to a lower age than the calendar age, in groups E of both men and women, fitness age was significantly higher compared to the calendar age. High fitness age represents a significant risk of morbidity in relation to non-communicable diseases and probably also a significant limitation of their quality of life in later age.

Slow increase of bilirubin concentration during administration of lenalidomide, bortezomib and dexamethasone for multiple myeloma (unmasking previously undiagnosed Gilbert syndrome) and disappearance of necrobiotic xanthogranuloma after complete remission of multiple myeloma.

BACKGROUND: Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. CASE DESCRIPTION: We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. CONCLUSION: NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

Diagnostic relevance of 18F-FDG PET/CT in newly diagnosed patients with monoclonal gammopathy of undetermined significance (MGUS): Single-center experience.

Monoclonal gammopathy of undetermined significance (MGUS) is a known precursor of more serious cancers, such as multiple myeloma (MM), Waldenström macroglobulinemia (MW) and other lymphoproliferative disorders. Using 18F-FDG PET/CT, we aimed to evaluate its benefit in early detection of various accompanying disorders and illnesses in MGUS patients. We prospectively analyzed the diagnostic relevance of 18F-FDG PET/CT in 390 newly diagnosed MGUS patients. On 18F-FDG PET/CT scans, the presence of focal or diffuse areas of detectable increased tracer uptake was recorded in 37 (9.5%) MGUS patients. The most frequent pathology was lymphadenopathy (3.8%), followed by thyroid diseases (2.1%), rheumatic diseases (1.8%), and other solid malignancies (1.5%). These results have major implications for confirmed associations of MGUS with numerous malignant and non-malignant disorders. We believe that 18F-FDG PET/CT imaging in newly diagnosed MGUS patients may be useful in early detection of other serious pathologies, not only in predicting progression of MGUS to active MM, and should be strongly recommended if available.

Bortezomib retreatment is effective in relapsed multiple myeloma patients - real-life clinical practice data.

Nowadays, bortezomib, a proteasome inhibitor, is widely used in treatment of newly diagnosed or relapsed multiple myeloma. The aim of this study was to analyze efficiency of bortezomib retreatment in patients with relapsed or refractory multiple myeloma. From 2004 to 2016, 283 patients were retrospectively evaluated at all hematological centers in the Czech Republic. Bortezomib was administered at the standard dosing and in combined therapy with corticosteroids, chemotherapy or thalidomide. Before bortezomib retreatment, 61% of patients received previous lenalidomide treatment, 40.6% autologous transplantation, and median number of prior lines of therapy was three. In total, 21% of patients were refractory to the first bortezomib treatment. In bortezomib retreatment, overall response rate was 34.5%, median progression-free survival was 7.8 months (95% CI: 6.7-8.9), median duration of response was 10.5 months (95% CI: 8.0-13.0) and median overall survival was 20.3 months (95% CI: 17.9-22.7). Grade 3-4 adverse events included thrombocytopenia, neutropenia, anemia and infection. Neuropathy grade 2 or higher occurred in 19.4% of patients. We conclude that bortezomib retreatment is an effective and safe therapeutic alternative for relapsed or refractory multiple myeloma patients.

Bortezomib and Thalidomide Treatment Results in Newly Diagnosed Transplant-Ineligible Multiple Myeloma Patients are Comparable in Long-Term Follow-Up.

BACKGROUND: Thalidomide-and bortezomib-containing regimens are widely used for transplant-ineligible newly diagnosed multiple myeloma patients. The aim of this study was to analyse the efficiency of thalidomide-or bortezomib-based regimens in long-term follow-up. MATERIALS AND METHODS: From 2008 to 2012, 142 transplant-ineligible newly diagnosed multiple myeloma patients were analysed retrospectively. Bortezomib was administered at the standard dosing of 1.3mg/m2 weekly, and thalidomide was administered at a daily dose of 100mg. Both drugs were combined with cyclophosphamide and dexamethasone. A total of 95 patients were treated with thalidomide and 47 with bortezomib. A median four cycles of treatment were administered in both groups. RESULTS: In the thalidomide group, the overall response rate was 60.6%, the median progression-free survival (PFS) was 10.3 months (95% CI 7.4-13.2) and the median overall survival (OS) was 35.1 months (95% CI 23.9-46.3). In the bortezomib group, the overall response rate was 51.1%, the median PFS was 11.9 months (95% CI 8.8-15) and the median OS was 25.4 months (95% CI 9.3-41.6). There was a statistically significant difference in OS (p = 0.027), favouring the cyclophosphamide/thalidomide/dexamethasone group, but the response rates and PFS intervals were not significantly different between both groups. The median follow-up in the thalidomide group was 35.1 months (95% CI 0.2-95.9) compared to 25.1 months (95% CI 0.4-60.6) in the bortezomib group (p = 0.004). The incidence of serious adverse events was comparable in both groups. CONCLUSION: In conclusion, the results of bortezomib treatment are comparable to thalidomide treatment under conditions of short administration. According to other clinical trials, long-term bortezomib treatment provides an additional advantage for PFS and OS.

Plasma Cell Leukemia ­â€Š the Forgotten Dis­ease

BACKGROUND: Plasma cell leukemia (PCL) is a rare dis-ease and possibly the most aggressive form of monoclonal gammopathy. It is classified into two forms -  primary PCL that occurs without a previously identifiable multiple myeloma stage, and secondary PCL that develops from previously dia-gnosed multiple myeloma. These two forms have different cytogenetic and molecular profiles, but both forms have an aggressive clinical course. Combinations of different therapeutic approaches includ-ing autologous stem cell transplantation and currently proteasome inhibitors and immunomodulatory drugs are used to treat PCL. Current dia-gnostic criteria, developed in the 1970s, may underestimate PCL prevalence; thus, prospective re-evaluation is be-ing considered. PURPOSE: The aim of this study is to review all available information about PCL with an emphasis on dia-gnostics, treatment, and circulat-ing plasma cells features. CONCLUSION: Although PCL is rare, it is quite a severe dis-ease. Current treatments us-ing the latest therapeutics have prolonged patient survival. However, due to the low incidence of PCL, information about the dis-ease is very limited and comes mostly from small retrospective studies. Further studies of PCL are needed, because new information could increase in patient survival and our understand-ing of its pathogenesis. Key words plasma cell leukemia -  multiple myeloma -  plasma cells -  cytogenetics -  treatment This work was supported by grant NV18-03-00203. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submited: 2. 11. 2018 Accepted: 18. 11. 2018.

Retreatment with lenalidomide is an effective option in heavily pretreated refractory multiple myeloma patients.

The combination of lenalidomide and dexamethasone is the current gold standard for treatment of relapsed multiple myeloma. This study analyzes the efficiency of repeated lenalidomide treatment in patients with relapsed and refractory multiple myeloma. A total of 41 patients were prospectively evaluated at the University Hospital Brno. Lenalidomide was administered at standard dosing and in combination with corticosteroids and/or chemotherapy. The maximum cumulative dose of lenalidomide was limited to 4,200 mg because of Czech health insurance rules. Before the second lenalidomide treatment, all patients were refractory to the last treatment; previously, 95% of patients had bortezomib treatment, 48% had autologous transplantation and the median number of prior therapy lines was three. A partial 14.2% or better response was achieved with the second lenalidomide treatment. The median progression-free survival was 4.8 months, and median overall survival was 11.9 months. Unfortunately, predicting risk factors in lenalidomide retreatment proved unsuccessful. Although our treatment results were significantly affected by limited Czech health care system coverage for lenalidomide, we established that its repeated treatment is an effective therapeutic alternative for heavily pretreated patients with relapsed and refractory multiple myeloma.

[MicroRNA Analysis for Extramedullary Multiple Myeloma Relapse]. / Analýza mikroRNA u extramedulárního relapsu mnohocetného myelomu.

INTRODUCTION AND AIMS: Multiple myeloma (MM) is the second most common hematooncological disease. Patient survival has been greatly improved by the introduction of new drugs into clinical practice, but survival is negatively affected by the so-called extramedullary relapse (EM), caused by the loss of plasma cell dependence on the bone marrow microenvironment and their migration out of the bone marrow. The nature and causes of this process are currently unclear. MicroRNAs (miRNAs) are short, non-coding RNA molecules involved in many physiological and pathological processes. Their significance in the pathogenesis of MM has been demonstrated by several studies. We assume that they are also involved in the development of the EM. The aim of this study was to analyze different miRNA expression between MM and EM patients. MATERIAL AND METHODS: Using next generation sequencing, we analyzed 39 samples of bone marrow cells from MM patients at diagnosis and 9 bone marrow plasma samples of EM patients. RESULTS: In total, 2,278 miRNA were sequenced, but only 658 miRNAs were analyzed as they were expressed in all samples and had at least 20 reads. Expression data were generated using the Chimira tool from fastq data. All sequences were mapped using miRBase v20. Further analyses were performed using the R/Bioconductor package. The Bayesian procedure was used for normalization of expression. P values were adjusted using the Benjamini-Hochberg method. Analysis found 10 miRNA (p < 0.0005) that are statistically significantly expressed in EM vs. MM patients - these are miR-26a-5p, miR-26b-5p, miR-30e-5p, miR-424-3p, miR-503-5p, miR-767-5p, miR-105-5p, miR-5695-5p, miR-450b-5p and miR-92b-3p. These miRNAs will be further verified by qPCR method on a larger set of MM and EM patients. CONCLUSION: Our pilot study has shown that there are differentially expressed miRNAs between MM and EM patients.Key words: multiple myeloma - microRNA - carcinogenesis - next generation sequencing The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papersThis work was supported by grant MZ CR AZV 17- 29343A. Submitted: 17. 3. 2018Accepted: 20. 3. 2018.

Liquid Biopsies - the Clinics and the Molecules.

Unlike bone marrow biopsies, liquid biopsies represent a gentler, more accessible, less painful, repeatable and more comprehensive approach to get biologically relevant information about the entire tumor but also about treatment response and level of minimal residual disease. This is all possible since peripheral blood contains not only circulating tumor cells but also many circulating molecules of nucleic acids (microRNA, cell-free DNA, long non-coding RNA etc.). Multiple myeloma is a genetically heterogeneous disease characterized by multifocal tumor deposits in the bone marrow but also focal lesions elsewhere. Single-site biopsy of the bone marrow creates a sampling bias that provides a limited molecular profile as the biopsy cannot capture all subclones. Moreover, during disease progression and treatment, molecular profile is changed and subclones of multiple myeloma cells resistant to treatment are formed. Likewise, various clones found in extramedullary sites that are not present in the bone marrow respond differently to treatment directly influencing survival of patients. Thus, liquid biopsies seem to be a relevant and necessary next step for diseases such as multiple myeloma.Key words: multiple myeloma - minimal residual disease - prognosis - liquid biopsies - cell-free DNA - non-coding RNA.

Type, intensity and duration of daily physical activities performed by adults with spinal cord injury.

STUDY DESIGN: Secondary analysis of cross-sectional data. OBJECTIVES: To describe and compare (1) self-reported intensities and durations of specific types of daily physical activities and (2) minutes per day spent on daily physical activities across key demographic groups. SETTING: Community (Ontario, Canada). METHODS: Participants were 695 adults with spinal cord injury (SCI; 76% male, Mage=46.81±13.41 years, Myears post injury=15.19±11.10 years). Daily activities were assessed over the telephone using the Physical Activity Recall Assessment for People with SCI. Multivariate analyses of variance (MANOVA) were computed to test for differences in intensities and durations of different daily activities (objective 1) and between-group differences in minutes per day of daily activities (objective 2). RESULTS: Overall, participants reported 127.92±142.79 min per day of daily physical activities with significantly more time spent in mild intensity (78.93±104.62 min per day) than moderate- (40.23±68.71 min per day) or heavy-intensity activities (8.75±24.53 min per day). Four patterns emerged with respect to type, duration and intensity, with some activities being typically performed at lighter or heavier intensities than others. There were significant differences in minutes per day of activity intensity and duration between groups based on education, injury severity and mode of mobility (P<0.05). CONCLUSION: Given that some groups were more likely to engage in moderate-heavy-intensity activities, and some activities were more likely to be performed at moderate-heavy intensities, interventions that target key groups to increase certain daily activities may be one strategy to enhance overall physical activity participation among people with SCI.

[Outcomes of AL-amyloidosis treatment with bortezomib, dexamethasone and cyclophosphamide or doxorubicin-containing regimens]. / Výsledky lécby AL-amyloidózy lécebnými rezimy obsahujícími bortezomib, dexametazon a dále cyklofosfamid anebo doxorubicin.

UNLABELLED: According to the criteria for multiple myeloma, systemic AL-amyloidosis may be divided into primary systemic AL-amyloidosis, where monoclonal gametopathy is present but the criteria for multiple myeloma are not satisfied, and systemic AL-amyloidosis with underlying multiple myeloma. There is a continuous transition between the two units. The present paper describes treatment of patients with established systemic AL-amyloidosis who satisfy the 2003 International Myeloma Working Groups criteria for symptomatic multiple myeloma (confirmed monoclonal immunoglobulin, clonal plasmocytes confirmed in the bone marrow and at least one clinical symptom of myeloma - confirmed amyloid). From 2009, a total of 10 patients with AL-amyloidosis and underlying multiple myeloma have been treated at our centre with combined bortezomib-containing regimens. The cohort includes 5 women and 5 men. Median age of these AL-amyloidosis patients at the diagnosis was 65.5 years. All 10 patients were treated with a combination of 3 drugs, bortezomib, cyclophosphamide and dexamethasone or bortezomib, doxorubicin a dexamethasone. Two of the 10 patients died during the first month of treatment. Treatment response cannot be evaluated in these patients. Haematological treatment response was evaluable in 8 patients only. Monoclonal immunoglobulin disappearance with negative urine and serum immunofixation and normalization of free light chain immunoglobulins was observed in six of the 8 patients. Treatment response according to the current IMWG was evaluated as very good partial remission (VGPR) as we did not perform bone marrow testing after the treatment to confirm complete remission according to the current criteria. One of the 8 evaluated patients died due to disease progression in the third month of treatment and there was no haematological treatment response in one who was considered to have a stable disease. Organ treatment response was evaluated in patients who were followed up for longer than 3 months of treatment only. Organ treatment response (reduced cardiac impairment) was not evaluable in a patient who had heart transplantation and then received chemotherapy. A total of 5 (83%) of the 6 evaluated patients fulfilled the criteria of organ treatment response. CONCLUSION: Our small cohort showed a high number of haematological treatment responses (VGPR in 75% of patients) as well as organ treatment response in patients with systemic AL-amyloidosis who were treated with bortezomib-containing treatment regimens.

Quantitative ballistocardiography (Q-BCG) for measurement of cardiovascular dynamics.

In the seventies of the past century ballistocardiography had been thought to be obsolete in cardiology for impossibility of objective calibration. In the present work the quantitative ballistocardiography (Q-BCG) for measurement of systolic force (F) and minute cardiac force (MF) in sitting subject was described. The new principle of piezoelectric transducer enabled to register the force caused by the heart and blood movement, which was not measured before. The calibration proved that the action of the force on the transducer was expressed quantitatively without the amplitude-, time-, and phase deformation. The close relationship of skeletal muscle force and F was proved. The F and MF changed under different physiological conditions (age, partial pressure of oxygen, body weight, skeletal muscle force). It was shown that the systolic force (F) and minute cardiac force (MF) are the physiological parameters neurohumorally regulated similarly as the heart rate or systolic volume.

Status of high current ion source operation at the GSI accelerator facility.

Vacuum arc ion sources, Penning ion sources, and filament driven multicusp ion sources are used for the production of high current ion beams of a variety of metallic and gaseous ions at the GSI accelerator facility. For accelerator operation, the ion sources have to provide a stable beam over a long period of time with an energy of 2.2 keV/u and a maximum mass over charge ratio of 65. The status of beam time operation at the high current injector is presented here giving an outline on important ion source data, such as ion beam current, ion beam spectrum, transversal emittance, life time, duty factor, and transmission along the low energy beam transport section.

Putative virulence-related genes in Vibrio anguillarum identified by random genome sequencing.

The genome of Vibrio anguillarum strain H775-3 was partially determined by a random sequencing procedure. A total of 2,300 clones, 2,100 from a plasmid library and 200 from a cosmid library, were sequenced and subjected to homology search by the BLAST algorithm. The total length of the sequenced clones is 1.5 Mbp. The nucleotide sequences were classified into 17 broad functional categories. Forty putative virulence-related genes were identified, 36 of which are novel in V. anguillarum, including a repeat in toxin gene cluster, haemolysin genes, enterobactin gene, protease genes, lipopolysaccharide biosynthesis genes, capsule biosynthesis gene, flagellar genes and pilus genes.

Cardiac contraction affects deep myocardial vessels predominantly.

To evaluate the roles of intramyocardial forces and systolic ventricular pressure in myocardial flow in the different layers separately, we measured myocardial flow in rabbit hearts during stable systolic contracture with left ventricular pressures of 60 (n = 5) and 0 mmHg (n = 5) and during stable diastolic arrest (n = 5). We also measured the number and size of the intramyocardial vessels after perfusion fixation (systolic arrest, n = 5; diastolic arrest, n = 5). In 25 rabbits, hearts were excised and perfused from the aortic root. Systolic arrest was achieved by perfusion of a low-Ca2+ Tyrode solution containing 2.0 mM Ba2+. Diastolic arrest was achieved by intraventricular injection of 700-1,000 mg pentobarbital sodium and was maintained by perfusion with St. Thomas cardioplegic solution. At perfusion pressure of 100 mmHg, subendocardial flow was lower than subepicardial flow during systolic arrest regardless of left ventricular pressure, whereas during diastolic arrest, subendocardial flow was higher than subepicardial flow. Subendocardial-to-subepicardial flow ratios for a physiological range of perfusion pressures were lower during systolic arrest with low rather than with high left ventricular pressure. Small arteriolar and capillary densities showed no difference between subendocardium and subepicardium. During systolic arrest, diameters of subendocardial terminal arterioles (4.6 +/- 1.3 microns) and capillaries (4.0 +/- 1.3 microns) were smaller than those in the subepicardium (8.8 +/- 1.7 and 7.1 +/- 1.6 microns, respectively; P less than 0.0001), whereas during diastolic arrest, diameters of subendocardial terminal arterioles (10.1 +/- 2.0 microns) and capillaries (7.6 +/- 1.8 microns) were slightly larger than those in the subepicardium (9.5 +/- 1.5 and 6.7 +/- 1.0 microns, respectively; P less than 0.01). We conclude that cardiac contraction predominantly affects subendocardial vessels and impedes subendocardial flow more than subepicardial flow regardless of left ventricular pressure.

Endometrial carcinoma, results of combined surgery and radiotherapy treatment of 93 patients (1979-1984).

A retrospective analysis was done on 93 cases with clinical stage I and II endometrial carcinoma. All patients in this series were treated by surgery and postoperative radiotherapy. Five-year survival reached 67%. No vaginal or vault recurrences were seen. Grade, stage and depth of myometrial invasion were prognostic parameters for survival, whereas 'age' did not show correlation with survival. Postoperative radiotherapy was performed by two different protocols, one of which appeared to be allied with significantly less late toxicity than the other.

Enzyme immunoassay for the detection of Giardia lamblia.

An enzyme immunoassay (EIA) was developed for direct detection of Giardia lamblia antigens in fecal specimens. The EIA was evaluated by testing specimens from 1,331 subjects in the USA and Egypt. For the 353 specimens from human subjects in the USA there was a 97% overall agreement between the results of the EIA and direct microscopic examination, yielding a sensitivity and specificity of 92% and 99% respectively. Due to adverse field conditions the EIA did not perform as well in the specimens collected and tested in Egypt. The sensitivity and specificity for 585 human specimens from Egypt were 74% and 97% respectively.