CAP Profiles

Bio

Academic Appointments

Honors & Awards

  • Distinguished Career Achievement Award, International Immunocompromised Host Society (ICHS) (2002)
  • Kenneth L. Vosti, M.D., Infectious Diseases Teaching Award, Stanford University School of Medicine (2002)
  • Albion Walter Hewlett Award, Stanford University (2002)
  • Infectious Diseases Divisional Teaching Award, Stanford University Department of Medicine (2002)
  • Fellow, American Academy of Microbiology (2000)
  • Fellow, American Association for the Advancement of Science (2000)
  • Ludwig Heilmeyer Society honorary membership, Ludwig Heilmeyer Society, Cologne, Germany (1998)
  • Bristol Award, Infectious Diseases Society of America (IDSA) (1996)
  • Diplomé de Docteur de L’Université Paul Sabatier de Toulouse DOCTEUR HONORIS CAUSA, l’Université Paul Sabatier, Toulouse, France (1992)
  • Harry A. Feldman Presidential Award, Infectious Diseases Society of America (IDSA) (1987-1988)
  • Alexander von Humboldt Scientific Award, Germany (1988)
  • MERIT Award, National Institutes of Health (1987)
  • James W. McLaughlin, MD Award, University of Texas (1985)
  • Maxwell Finland Award, Infectious Diseases Society of America (IDSA) (1982)
  • Osler Oration and Gold Medal, Royal College of Physicians, London, England (1999)
  • Award/Gold Medal, Dr.-Friedrich-Sasse-Foundation, Berlin, Germany (1999)
  • Fellowship, Royal College of Physicians, London, England (1999)
  • "Achievement in Medicine" Award, Santa Clara County Medical Association (1993)
  • Fellows Award for Clinical Excellence, Stanford University School of Medicine (1973)

Professional Education

  • Board Certif., ID, Amer. Brd. of Internal Med.
  • Fellowship, Harvard Medical School, Infectious Diseases (1962)
  • Resident, UCSF Medical Center, SF, Internal Medicine/ID (1960)
  • MD, Univers. of IL Coll. of Medicine, Internal Medicine (1956)

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Research & Scholarship

Current Research and Scholarly Interests

Studies on the diagnosis, epidemiology, clinical features and prevention of toxoplasmosis in the pregnant woman, the fetus and newborn, in eye disease and in the immunocompromised patient.

Teaching

Graduate and Fellowship Programs

Publications

All Publications

  • Polymerase chain reaction in cerebrospinal fluid for the diagnosis of congenital toxoplasmosis. Pediatric infectious disease journal Olariu, T. R., Remington, J. S., Montoya, J. G. 2014; 33 (6): 566-570

    Abstract

    Congenital toxoplasmosis (CT) can result in visual impairment, hearing loss, serious neurologic sequelae and death in the infant. We studied the potential of the polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) for diagnosis of congenital toxoplasmosis.For this purpose we studied both congenitally infected (diagnosed clinically and serologically) and non-infected infants born to untreated mothers.The infants ranged in age from 0 to 180 days. CSF PCR was positive in 27 of the 58 (46.5%) congenitally infected infants and was negative in each of the 103 infants without CT. The frequency of positive CSF PCR varied according to whether infants had major clinical signs of the disease; PCR was positive in 70.9%, 53.3% and 50.9% of those with hydrocephalus, cerebral calcifications and/or eye disease, respectively. Three of six infants who were negative for both IgM and IgA antibodies had a positive PCR in their CSF as the confirmatory test for diagnosis of congenital toxoplasmosis. IgM and IgA antibodies and CSF PCR, when combined, yielded a higher sensitivity for diagnosis of congenital toxoplasmosis when compared with the performance of each test alone.Our findings reveal that in infants with clinical and serologic findings suggestive of congenital toxoplasmosis and born to untreated mothers, CSF PCR has the potential to increase the frequency of cases in which the diagnosis is confirmed.

    View details for DOI 10.1097/INF.0000000000000256

    View details for PubMedID 24445828

  • Severe Congenital Toxoplasmosis in the United States Clinical and Serologic Findings in Untreated Infants PEDIATRIC INFECTIOUS DISEASE JOURNAL Olariu, T. R., Remington, J. S., McLeod, R., Alam, A., Montoya, J. G. 2011; 30 (12): 1056-1061

    Abstract

    Congenital toxoplasmosis can cause significant neurologic manifestations and other untoward sequelae.The Palo Alto Medical Foundation Toxoplasma Serology Laboratory database was searched for data on infants 0 to 180 days old, in whom congenital toxoplasmosis had been confirmed and who had been tested for Toxoplasma gondii-specific immunoglobulin G (IgG), IgM, and IgA antibodies, between 1991 and 2005. Their clinical findings were confirmed at the National Collaborative Chicago-based Congenital Toxoplasmosis Study center. We reviewed available clinical data and laboratory profiles of 164 infants with congenital toxoplasmosis whose mothers had not been treated for the parasite during gestation.One or more severe clinical manifestations of congenital toxoplasmosis were reported in 84% of the infants and included eye disease (92.2%), brain calcifications (79.6%), and hydrocephalus (67.7%). In 61.6% of the infants, eye disease, brain calcifications, and hydrocephalus were present concurrently. T. gondii-specific IgM, IgA, and IgE antibodies were demonstrable in 86.6%, 77.4%, and 40.2% of the infants, respectively. Testing for IgM and IgA antibodies increased the sensitivity of making the diagnosis of congenital toxoplasmosis to 93% compared with testing for IgM or IgA individually. IgM and IgA antibodies were still present in 43.9% of infants diagnosed between 1 and 6 months of life.Our study reveals that severe clinical signs of congenital toxoplasmosis including hydrocephalus, eye disease, or intracranial calcifications occurred in 85% infants whose sera were referred to our reference Toxoplasma Serology Laboratory during a period of 15 years. Laboratory tests, including serologic and polymerase chain reaction tests, were critical for diagnosis in the infants. Our results contrast remarkably with those of European investigators who rarely observe severe clinical signs in infants with congenital toxoplasmosis.

    View details for DOI 10.1097/INF.0b013e3182343096

    View details for Web of Science ID 000297406100012

    View details for PubMedID 21956696

  • Risk Factors for Toxoplasma gondii Infection in the United States CLINICAL INFECTIOUS DISEASES Jones, J. L., Dargelas, V., Roberts, J., Press, C., Remington, J. S., Montoya, J. G. 2009; 49 (6): 878-884

    Abstract

    Toxoplasmosis can cause severe ocular and neurological disease. We sought to determine risk factors for Toxoplasma gondii infection in the United States.We conducted a case-control study of adults recently infected with T. gondii. Case patients were selected from the Palo Alto Medical Foundation Toxoplasma Serology Laboratory from August 2002 through May 2007; control patients were randomly selected from among T. gondii-seronegative persons. Data were obtained from serological testing and patient questionnaires.We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef (adjusted odds ratio [aOR], 6.67; 95% confidence limits [CLs], 2.09, 21.24; attributable risk [AR], 7%); eating rare lamb (aOR, 8.39; 95% CLs, 3.68, 19.16; AR, 20%); eating locally produced cured, dried, or smoked meat (aOR, 1.97; 95% CLs, 1.18, 3.28; AR, 22%); working with meat (aOR, 3.15; 95% CLs, 1.09, 9.10; AR, 5%); drinking unpasteurized goat's milk (aOR, 5.09; 95% CLs, 1.45, 17.80; AR, 4%); and having 3 or more kittens (aOR, 27.89; 95% CLs, 5.72, 135.86; AR, 10%). Eating raw oysters, clams, or mussels (aOR, 2.22; 95% CLs, 1.07, 4.61; AR, 16%) was significant in a separate model among persons asked this question. Subgroup results are also provided for women and for pregnant women.In the United States, exposure to certain raw or undercooked foods and exposure to kittens are risk factors for T. gondii infection. Knowledge of these risk factors will help to target prevention efforts.

    View details for DOI 10.1086/605433

    View details for Web of Science ID 000269145100008

    View details for PubMedID 19663709

  • Management of Toxoplasma gondii infection during pregnancy CLINICAL INFECTIOUS DISEASES Montoya, J. G., Remington, J. S. 2008; 47 (4): 554-566

    Abstract

    Acute infection with Toxoplasma gondii during pregnancy and its potentially tragic outcome for the fetus and newborn continue to occur in the United States, as well as worldwide, despite the fact that it can be prevented. The infection can be acquired through ingestion of infected, undercooked meat or contaminated food or water. Transmission to the fetus occurs almost solely in women who acquire their primary infection during gestation and can result in visual and hearing loss, mental and psychomotor retardation, seizures, hematological abnormalities, hepatosplenomegaly, or death. Systematic education and serological screening of pregnant women are the most reliable and currently available strategies for the prevention, diagnosis, and early treatment of the infection in the offspring; this is largely because toxoplasmosis in pregnant women most often goes unrecognized. Treatment of the infection in the fetus and infant during the first year of life has been demonstrated to significantly improve the clinical outcome.

    View details for DOI 10.1086/590149

    View details for Web of Science ID 000257755700023

    View details for PubMedID 18624630

  • Prevalence of infection with Toxoplasma gondii among pregnant women in Cali, Colombia, South America AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Rosso, F., Les, J. T., Agudelo, A., Villalobos, C., Chaves, J. A., Tunubala, G. A., Messa, A., Remington, J. S., Montoya, J. G. 2008; 78 (3): 504-508

    Abstract

    The aim of this study was to determine the prevalence of toxoplasma antibodies among pregnant women in Cali, Colombia. In 2005, 955 pregnant women were tested for IgG and IgM antibodies and sociodemographic information was collected. Their average age was 25.1 years, overall IgG seroprevalence 45.8% (95% CI: 41.8%, 48.2%), IgM 2.8% (95% CI: 1.5%, 3.6%). Seroprevalence increased significantly with age, 39.0% in 14 to 19 years to 55.3% in 30 to 39 years (P = 0.001). There was a significant trend toward a higher seroprevalence in the lower socioeconomic strata (SES) (low: 49.0%, high: 29%, P = 0.004). The increase in seroprevalence by age was more significant in the lower socioeconomic strata (P = 0.002). Our results suggest a higher prevalence when compared with those of the national 1980 (33-37.6%) survey. In contrast to reports from other regions of the world, Cali has not seen a decrease in T. gondii seroprevalence over the past 25 years.

    View details for Web of Science ID 000253928100027

    View details for PubMedID 18337350

  • The differential agglutination test as a diagnostic aid in cases of toxoplasmic lymphadenitis JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Berry, A., Rosso, F., Remington, J. S. 2007; 45 (5): 1463-1468

    Abstract

    Lymphadenopathy (LN) is the most common clinical manifestation of acute acquired toxoplasma infection in humans. The diagnosis of toxoplasmic lymphadenitis (TL) is established by serological methods and/or lymph node biopsy. In the United States, the differential agglutination (of acetone [AC]-fixed versus that of formalin [HS]-fixed tachyzoites) test (AC/HS test) has primarily been used in assessments of pregnant women as a component of the toxoplasma serological profile to distinguish between recently acquired infections and infections acquired in the distant past. We studied the AC/HS test in patients with TL to define its usefulness in diagnosing individuals presenting with LN and to determine its kinetics after the onset of LN. One hundred nine consecutive patients (158 serum samples) diagnosed serologically and by lymph node biopsy as having TL were studied. Specific patterns in the AC/HS test were noted to be dependent on the time from the clinical onset of LN (COLN). Acute AC/HS patterns were observed for more than 75% of patients who according to their histories had developed their TL within 6 months after COLN. Acute patterns were not observed beyond the 12th month except for a single patient for whom an acute pattern (400/800) persisted to the 13th month after COLN. Equivocal patterns were observed up to 36 months after COLN. Nonacute patterns were observed only for serum samples drawn at least 13 months after COLN. A nonacute pattern in an individual at less than 12 months after COLN should suggest an etiology other than TL. In such cases, investigation for alternative causes, including malignancy, should be instigated.

    View details for DOI 10.1128/JCM.01781-06

    View details for Web of Science ID 000246600300013

    View details for PubMedID 17314220

  • Use of a single serum sample for diagnosis of acute toxoplasmosis in pregnant women and other adults JOURNAL OF CLINICAL MICROBIOLOGY Press, C., Montoya, J. G., Remington, J. S. 2005; 43 (7): 3481-3483

    Abstract

    Using a single serum sample for testing for immunoglobulin G (IgG) Toxoplasma antibodies, differences in sensitivity of the dye test (which measures primarily IgG antibodies) and an IgG enzyme immunoassay were found useful for very early diagnosis of acute Toxoplasma gondii infection.

    View details for DOI 10.1128/JCM.43.7.3481-3483.2005

    View details for Web of Science ID 000230614900075

    View details for PubMedID 16000484

  • Evaluation of the immunoglobulin G avidity test for diagnosis of toxoplasmic lymphadenopathy JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Huffman, H. B., Remington, J. S. 2004; 42 (10): 4627-4631

    Abstract

    Toxoplasmic lymphadenopathy (TL) is the most common clinical manifestation of acute acquired toxoplasma infection in normal individuals. The diagnosis is established by serologic methods and lymph node biopsy. Recently, tests for avidity of toxoplasma immunoglobulin G (IgG) antibodies have been introduced to help discriminate between recently acquired and distant infection with the parasite. We studied an avidity test to define the usefulness of this method and to determine the evolution of the IgG avidity in TL. Seventy-three consecutive patients diagnosed as having TL were studied. IgG avidity test titers were noted to be time dependent from the clinical onset of lymphadenopathy. Low IgG avidity test results were observed in patients who had developed lymphadenopathy from <1 month to 17 months prior to the sampling of sera, emphasizing that low IgG avidity test results are not reliable for diagnosis of recently acquired infection. In contrast, high IgG avidity test results were observed only in patients who had developed lymphadenopathy at least 4 months earlier. Thus, a high IgG avidity test result in an individual who has recent onset of lymphadenopathy (e.g., within 2 to 3 months of sera sampling) suggests a cause other than toxoplasmosis. In such cases, further workup is warranted in order to determine the cause of the lymphadenopathy.

    View details for DOI 10.1128/JCM.42.10.4627-4631.2004

    View details for Web of Science ID 000224473000033

    View details for PubMedID 15472320

  • Management of community-acquired respiratory tract infections CLINICAL INFECTIOUS DISEASES Remington, J. S. 2004; 39: S141-S141

    View details for Web of Science ID 000223367700001

    View details for PubMedID 15546108

  • Recent developments for diagnosis of toxoplasmosis JOURNAL OF CLINICAL MICROBIOLOGY Remington, J. S., Thulliez, P., Montoya, J. G. 2004; 42 (3): 941-945

    View details for DOI 10.1125/JCM.42.3.941-945.2004

    View details for Web of Science ID 000220376900001

    View details for PubMedID 15004036

  • TCR V beta 8(+) T cells prevent development of toxoplasmic encephalitis in BALB/c mice genetically resistant to the disease JOURNAL OF IMMUNOLOGY Kang, H., Liesenfeld, O., Remington, J. S., Claflin, J., Wang, X. S., Suzuki, Y. 2003; 170 (8): 4254-4259

    Abstract

    BALB/c are genetically resistant to development of toxoplasmic encephalitis (TE) when infected with Toxoplasma gondii, whereas CBA/Ca mice are susceptible. We compared TCR Vbeta chain usage in lymphocytes infiltrated into brains between these animals following infection. TCR Vbeta8(+) cells were the most frequent T cell population in brains of infected, resistant BALB/c mice, whereas TCR Vbeta6(+) T cells were more prevalent than Vbeta8(+) T cells in brains of infected, susceptible CBA/Ca mice. Adoptive transfer of Vbeta8(+) immune T cells, obtained from infected BALB/c mice, prevented development of TE and mortality in infected athymic nude mice that lack T cells. In contrast, adoptive transfer of Vbeta6(+) immune T cells did not prevent development of TE or mortality in the nude mice. The protective activity of Vbeta8(+) immune T cells was greater than that of the total Vbeta8(-) population. In addition, Vbeta8(+) immune T cells produced markedly greater amounts of IFN-gamma than did the Vbeta8(-) population after stimulation with tachyzoite lysate Ags in vitro. Thus, Vbeta8(+) T cells appear to play a crucial role in the genetic resistance of BALB/c mice against development of TE.

    View details for Web of Science ID 000182171100040

    View details for PubMedID 12682259

  • VIDAS test for avidity of Toxoplasma-specific immunoglobulin G for confirmatory testing of pregnant women JOURNAL OF CLINICAL MICROBIOLOGY Montoya, J. G., Liesenfeld, O., Kinney, S., Press, C., Remington, J. S. 2002; 40 (7): 2504-2508

    Abstract

    Because congenital toxoplasmosis is almost solely the result of maternal infection acquired during gestation, it is critical to determine whether infection during pregnancy has occurred. In the United States, definitive diagnosis of the acute infection and the time of its occurrence have been compromised by a lack of systematic screening and the fact that only a single serum sample is submitted for testing. In studies in Europe, and depending on the method used, the demonstration of high-avidity immunoglobulin G (IgG) toxoplasma antibodies has been shown to exclude infection having occurred in the first 3 to 5 months of pregnancy. We investigated the usefulness of determining the avidity of IgG toxoplasma antibodies with a VIDAS kit (herein referred to as the VIDAS Toxo-IgG avidity kit, the VIDAS kit essentially rules out acute infection having occurred within the 4 prior months) in the setting of a reference serology laboratory in the United States. Sera (132 samples) from 132 women in the first 16 weeks of pregnancy were chosen because at least one test in the toxoplasma serological profile (TSP) suggested or was equivocal for a recently acquired infection. High-avidity antibodies were demonstrated in 75% of 99 sera positive with the IgM enzyme-linked immunosorbent assay (ELISA) and 31.3% of 16 sera with acute TSP results. A significant percentage of sera with equivocal results wtih the IgM ELISA or TSP also had high-avidity test results. Of 39 women for whom treatment with spiramycin had been suggested to attempt to prevent congenital transmission, 19 (48.7%) had high-avidity antibodies. These findings highlight the value of the VIDAS IgG avidity kit when used in combination with the TSP to exclude recent infection, especially when only a single serum sample is available.

    View details for DOI 10.1128/JCM.40.7.2504-2508.2002

    View details for Web of Science ID 000176605800030

    View details for PubMedID 12089270

  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infections in the Immunocompromised Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hung, S., Giannetti, N., Miller, J., Remington, J. S. OXFORD UNIV PRESS INC. 2001: 629–40

    Abstract

    A total of 1073 infectious episodes (IEs) that occurred in 620 consecutive heart transplantation patients at Stanford Medical Center between 16 December 1980 and 30 June 1996 were reviewed. Infectious complications were a major cause of morbidity and mortality, second only to rejection as the cause of early deaths and the most common cause of late deaths. Of the IEs, 468 (43.6%) were caused by bacteria, 447 (41.7%) by viruses, 109 (10.2%) by fungi, 43 (4.0%) by Pneumocystis carinii, and 6 (0.6%) by protozoa. The largest number of IEs occurred in the lungs (301 [28.1%]). A significant reduction in the incidence of IEs and a delay in presentation after transplantation were observed; these were most likely related to the introduction of new chemoprophylactic regimens during the study period and prevention of significant disease caused by cytomegalovirus.

    View details for Web of Science ID 000170271200007

    View details for PubMedID 11486285

  • Infectious complications among 620 consecutive heart transplant patients at Stanford University Medical Center 10th International Symposium on Infection in the Immunocompromised Host Montoya, J. G., Giraldo, L. F., Efron, B., Stinson, E. B., Gamberg, P., Hunt, S., Giannetti, N., Miller, J., Remington, J. S. CELL PRESS. 2001: 629–U6

    View details for Web of Science ID 000170271400014

  • Simple and efficient method for measuring anti-toxoplasma immunoglobulin antibodies in human sera using complement-mediated lysis of transgenic tachyzoites expressing beta-galactosidase JOURNAL OF CLINICAL MICROBIOLOGY Dando, C., Gabriel, K. E., Remington, J. S., Parmley, S. F. 2001; 39 (6): 2122-2125

    Abstract

    A simple and efficient method using transgenic Toxoplasma gondii tachyzoites expressing beta-galactosidase was developed for detection of specific antibodies against the parasite in sera of patients. The titers obtained with the new test were similar to those obtained with the Sabin-Feldman dye test run in parallel. Although significant changes in endpoint titers were not observed when sera drawn sequentially at 2- to 3-week intervals were tested with both procedures, apparent differences in antibody affinity were observed with the new test which were not perceptible with the Sabin-Feldman dye test. Like the Sabin-Feldman dye test, the new test is based on complement lysis of tachyzoites, but it is much easier to perform and the reaction is read colorimetrically instead of visually.

    View details for Web of Science ID 000169097100014

    View details for PubMedID 11376045

  • Detection of immunoglobulin m antibodies to p35 antigen of Toxoplasma gondii for serodiagnosis of recently acquired infection in pregnant women JOURNAL OF CLINICAL MICROBIOLOGY Suzuki, Y., Ramirez, R., Press, C., Li, S. L., Parmley, S., Thulliez, P., Remington, J. S. 2000; 38 (11): 3967-3970

    Abstract

    We examined the efficiency of detection of immunoglobulin M (IgM) antibodies to a 35-kDa antigen (P35) of Toxoplasma gondii for serodiagnosis of acute infection in pregnant women. A double-sandwich enzyme-linked immunosorbent assay (ELISA) with recombinant P35 antigen (P35-IgM-ELISA) was used for this purpose. On the basis of the clinical history and the combination of results from the toxoplasma serological profile (Sabin-Feldman dye test, conventional IgM and IgA ELISAs, and the differential agglutination test), the patients were classified into three groups: group I, status suggestive of recently acquired infection; group II, status suggestive of infection acquired in the distant past; group III, status suggestive of persisting IgM antibodies. Eighteen (90.0%) of 20 serum samples from group I patients were positive by the P35-IgM-ELISA, whereas none of the 33 serum samples from group II patients were positive. Only 4 (25.0%) of 16 serum samples from group III patients were positive by the P35-IgM-ELISA, whereas all these serum samples were positive by the conventional IgM ELISA. These results indicate that demonstration of IgM antibodies against P35 by the P35-IgM-ELISA is more specific for the acute stage of the infection than demonstration of IgM antibodies by the ELISA that uses a whole-lysate antigen preparation. Studies with sera obtained from four pregnant women who seroconverted (IgG and IgM antibodies) during pregnancy revealed that two of them became negative by the P35-IgM-ELISA between 4 and 6 months after seroconversion, whereas the conventional IgM ELISA titers remained highly positive. The P35-IgM-ELISA appears to be useful for differentiating recently acquired infection from those acquired in the distant past in pregnant women.

    View details for Web of Science ID 000166892900010

    View details for PubMedID 11060053

  • Protection against lipopolysaccharide-induced death by fluoroquinolones ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Khan, A. A., Slifer, T. R., Araujo, F. G., Suzuki, Y., Remington, J. S. 2000; 44 (11): 3169-3173

    Abstract

    Because fluoroquinolones have an immunomodulatory effect on cytokine production by lipopolysaccharide (LPS)-treated human monocytes, we examined the effect of fluoroquinolones on the survival of mice injected with a lethal dose of LPS. Trovafloxacin (100 mg/kg), ciprofloxacin (250 mg/kg), and tosufloxacin (100 mg/kg) protected 75% (P = 0.0001), 25% (P = 0.002), and 50% (P = 0.002), respectively, of mice against death. The fluoroquinolones significantly reduced serum levels of interleukin-6 and tumor necrosis factor alpha in LPS-treated mice. The protective effects of fluoroquinolones in LPS-induced shock in mice may also occur in humans.

    View details for Web of Science ID 000090029200043

    View details for PubMedID 11036044

  • Ketolide ABT-773 is active against Toxoplasma gondii JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Khan, A. A., Araujo, F. G., Craft, J. C., Remington, J. S. 2000; 46 (3): 489-492

    Abstract

    ABT-773 is active in vitro and in vivo against Toxoplasma gondii. It inhibited replication of RH strain tachyzoites in human foreskin fibroblasts. Mice infected intraperitoneally with tachyzoites and treated orally with 25, 50 or 100 mg/kg/day of ABT-773 for 10 days had 20% (P: = 0.016), 50% (P: = 0.003) and 100% (P: = 0.001) survival, respectively. Remarkable and highly significant survival was also noted in mice infected orally with strain C56 cysts and treated with ABT-773. Thus, ABT-773 may be useful for therapy of human toxoplasmosis.

    View details for Web of Science ID 000089299600023

    View details for PubMedID 10980181

  • Serodiagnosis of recently acquired Toxoplasma gondii infection using an enzyme-linked immunosorbent assay with a combination of recombinant antigens CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY Li, S. L., Galvan, G., Araujo, F. G., Suzuki, Y., Remington, J. S., Parmley, S. 2000; 7 (5): 781-787

    Abstract

    An enzyme-linked immunosorbent assay (ELISA) using four recombinant antigens of Toxoplasma gondii (rP22, rP25, rP29, and rP35) was used in an attempt to differentiate pregnant women with toxoplasma serologic profiles (TSPs) indicative of recently acquired infections (acute profile) from those with TSPs indicative of infections acquired in the distant past (chronic profile). In general, immunoglobulin G antibodies in sera from women with the acute profile reacted more strongly with the recombinant antigens than did those in sera from women with the chronic profile. However, reactivities differed significantly between antigens that reacted with a single serum and between sera that reacted with a single antigen. Because of these variations, we employed a combination of the four antigens in an ELISA (Comb-ELISA) and evaluated its ability to distinguish pregnant women with the acute profile from those with the chronic profile. Eighteen of 20 (90%) sera from acute-profile women were positive in the Comb-ELISA, whereas 69 of 70 (98.6%) sera from the chronic-profile women were negative. Thus, the Comb-ELISA may be useful for diagnosis of toxoplasmosis in pregnant women and for differentiation between recently acquired infections and infections acquired in the more distant past.

    View details for Web of Science ID 000089235400013

    View details for PubMedID 10973455

  • Strategies for the successful treatment of gram-positive bacterial infections CLINICAL INFECTIOUS DISEASES Remington, J. S. 2000; 31: S150-S151

    View details for Web of Science ID 000090150600006

    View details for PubMedID 11017865

  • Effect of quinupristin/dalfopristin on production of cytokines by human monocytes JOURNAL OF INFECTIOUS DISEASES Khan, A. A., Slifer, T. R., Araujo, F. G., Remington, J. S. 2000; 182 (1): 356-358

    Abstract

    The effect of the novel streptogramin antibiotic quinupristin/dalfopristin (synercid) on cytokine production in vitro was examined in monocytes obtained from healthy human volunteers and stimulated with either lipopolysaccharide or heat-killed Staphylococcus aureus (Pansorbin). Synercid at concentrations that are achievable in humans (1, 5, and 10 microgram/mL) significantly suppressed production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha in a concentration-dependent manner. Thus, synercid possesses significant immunomodulatory activity, in addition to its antimicrobial activity.

    View details for Web of Science ID 000088522300051

    View details for PubMedID 10882624

  • Decreased resistance of B cell-deficient mice to infection with Toxoplasma gondii despite unimpaired expression of IFN-gamma, TNF-alpha, and inducible nitric oxide synthase JOURNAL OF IMMUNOLOGY Kang, H., Remington, J. S., Suzuki, Y. 2000; 164 (5): 2629-2634

    Abstract

    The role of B cells in resistance against Toxoplasma gondii was studied using B cell-deficient (muMT) mice. Following peroral infection with 10 cysts of the ME49 strain, all muMT mice survived the acute stage of the infection but died between 3 and 4 wk after infection. In contrast, all control mice were alive at 8 wk after infection. At the stage during which muMT animals succumbed to the infection, parasite replication and pathology were most evident in their brains; small numbers of tachyzoites were also detectable in their lungs. Significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of muMT than in control mice. Large areas of necrosis associated with numerous tachyzoites were observed only in brains of muMT mice. Anti-T. gondii IgG Abs were detected only in sera of control mice, whereas similar levels of IFN-gamma were detected in sera of both strains of mice. Amounts of mRNA for IFN-gamma, IL-10, and inducible NO synthase in the brain did not differ between infected muMT and control mice. Expression of mRNA for TNF-alpha was increased in brains of muMT mice. Administration of polyclonal rabbit anti-T. gondii IgG Ab prevented early mortality and pathology associated with tachyzoites in the brain in the infected muMT mice. These results indicate that B cells play an important role, most likely through their production of specific Abs, in resistance to persistent active (tachyzoite) infection with T. gondii in mice, especially in the brain and lung.

    View details for Web of Science ID 000085477100044

    View details for PubMedID 10679102

  • Introduction Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Remington, J. S. 2000; 31 Suppl 4: S123

    View details for DOI 10.1086/314076

    View details for PubMedID 11017860

  • Use of ketolides in combination with other drugs to treat experimental toxoplasmosis JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY Araujo, F. G., Khan, A. A., Bryskier, A., Remington, J. S. 1998; 42 (5): 665-667

    Abstract

    Because combination therapy is required to treat human toxoplasmosis, we examined combinations of the ketolides HMR 3004 and HMR 3647 with atovaquone, clindamycin or sulphadiazine in a murine model of toxoplasmosis. An oral dose of 50 mg/kg/day of HMR 3004 protected 30% of mice lethally infected with Toxoplasma gondii. The same dose protected 100% of infected mice when administered in combination with non-protective doses of atovaquone, clindamycin or sulphadiazine. Similar results were noted with 25 mg/kg/day of HMR 3647. These results demonstrate that these drug combinations are highly effective for treating toxoplasmosis in mice.

    View details for Web of Science ID 000077186400017

    View details for PubMedID 9848454

  • Scedosporium apiospermum (Pseudallescheria boydii) infection in a heart transplant recipient: A case of mistaken identity JOURNAL OF HEART AND LUNG TRANSPLANTATION Lopez, F. A., Crowley, R. S., Wastila, L., Valantine, H. A., Remington, J. S. 1998; 17 (3): 321-324

    Abstract

    We report a case of fatal central nervous system infection with Scedosporium apiospermum (Pseudallescheria boydii) in a heart transplant recipient. This ubiquitous fungus is known to cause mycetoma and localized infections in patients with otherwise normal conditions. Disseminated infections occur rarely and are seen primarily in patients who are receiving immunosuppressive medications or who have neutropenia. Often life-threatening when infection is disseminated and involves the central nervous system, this diagnosis is difficult to make rapidly because S. apiospermum (P. boydii) mimics Aspergillus spp. and Fusarium spp., both clinically and histopathologically. Imidazoles such as miconazole, but not amphotericin B, are considered the therapeutic compounds of choice. Improved diagnostic and treatment options are needed to optimize management of infections with S. apiospermum (P. boydii).

    View details for Web of Science ID 000072988500013

    View details for PubMedID 9563611

  • Impaired resistance to the development of toxoplasmic encephalitis in interleukin-6-deficient mice INFECTION AND IMMUNITY Suzuki, Y., Rani, S., Liesenfeld, O., Kojima, T., Lim, S., Nguyen, T. A., Dalrymple, S. A., Murray, R., Remington, J. S. 1997; 65 (6): 2339-2345

    Abstract

    The role of interleukin-6 (IL-6) in the pathogenesis of toxoplasmic encephalitis (TE) was examined by using IL-6-targeted mutant (IL-6(-/-)) mice. At 4 and 8 weeks after infection with the ME49 strain of Toxoplasma gondii, significantly greater numbers of T. gondii cysts and areas of inflammation associated with tachyzoites were observed in brains of IL-6(-/-) mice than in those of control mice. Large areas of necrosis were observed only in brains of IL-6(-/-) mice. Tachyzoites were frequently detected in the areas of necrosis, suggesting that necrosis was caused by proliferation of the parasite. These results indicate that IL-6 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in brains of infected mice. Whereas in brains of control mice, large numbers of inflammatory cells were always observed in areas where tachyzoites were detected, in brains of IL-6(-/-) mice, only small numbers of inflammatory cells were observed in many areas with tachyzoites. Lymphocyte preparations isolated from brains of infected control mice had significantly higher ratios of gamma/delta T cells and CD4+ alpha/beta T cells but lower ratios of CD8+ alpha/beta T cells compared to those of infected IL-6(-/-) mice. There were no differences in the ratios of these T-cell subsets in spleens between these mice. The amounts of mRNA for gamma interferon (IFN-gamma) detected by reverse transcriptase PCR were significantly smaller in brains of IL-6(-/-) mice than in those of control mice, whereas amounts of IL-10 mRNA were greater in the former than in the latter. IL-6 mRNA was detected only in infected control mice. The protective activity of IL-6 against development of TE appears to be through its ability to stimulate IFN-gamma production and induce infiltration and accumulation of different T-cell subsets in brains of infected mice.

    View details for Web of Science ID A1997XB56200050

    View details for PubMedID 9169772

    View details for PubMedCentralID PMC175324

  • Treatment with interleukin 12 in combination with atovaquone or clindamycin significantly increases survival of mice with acute toxoplasmosis ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Hunter, C. A., Remington, J. S. 1997; 41 (1): 188-190

    Abstract

    The capacity of interleukin 12 (IL-12) to potentiate drugs in the treatment of murine toxoplasmosis was examined. IL-12 (100 ng/injection), atovaquone (10 mg/kg of body weight/day), or clindamycin (5 mg/kg/day) administered alone caused delayed time to death or minimal survival rates. In contrast, significant survival rates resulted when the same dose of IL-12 was used in combination the same doses of atovaquone (P=0.01) or clindamycin (P=0.001). Infected mice treated with IL-12 plus drug produced significantly higher levels of gamma interferon than controls. Although IL-12 was effective only when administered before infection, these results suggest that this cytokine may be a useful adjunct in the therapy of human toxoplasmosis in situations when cysts reactivate and tachyzoites start multiplying in immunocompromised patients.

    View details for Web of Science ID A1997WA65600034

    View details for PubMedID 8980778

  • Macrolides, azalides, and streptogramins in treatment of opportunistic infections in immunocompromised patients 3rd International Conference on the Macrolides, Azalides, and Streptogramins Remington, J. S. MARCEL DEKKER. 1997: 189–204

    View details for Web of Science ID A1997BJ12K00014

  • Tularemia presenting as community-acquired pneumonia - Implications in the era of managed care ARCHIVES OF INTERNAL MEDICINE Fredricks, D. N., Remington, J. S. 1996; 156 (18): 2137-2140

    Abstract

    A case of pleuropulmonary tularemia was diagnosed by sputum culture and serologic studies in a patient who did not have classic epidemiological risks for tularemia. The patient had atypical pneumonia when initially seen and his condition slowly improved with antibiotic therapy that included erythromycin lactobionate. The diagnosis of tularemia was delayed because the gram-negative rod isolated from the patient's sputum was initially not speciated in an effort to reduce laboratory costs.

    View details for Web of Science ID A1996VL78200015

    View details for PubMedID 8862107

  • Rifapentine is active in vitro and in vivo against Toxoplasma gondii ANTIMICROBIAL AGENTS AND CHEMOTHERAPY Araujo, F. G., Khan, A. A., Remington, J. S. 1996; 40 (6): 1335-1337

    Abstract

    Rifapentine, a derivative of rifamycin, was examined for its in vitro and in vivo activities against the protozoan parasite Toxoplasma gondii. The drug inhibited the intracellular replication of parasites and was not cytotoxic for the host cells at inhibitory concentrations. Mice infected either intraperitoneally with tachyzoites of the RH strain or orally with tissue cysts of the C56 strain were protected against death by treatment with rifapentine. The degree of protection was similar to that induced by atovaquone and apparently higher than that induced by rifabutin. Rifapentine may be a useful drug for the treatment of toxoplasmosis in immunocompromised individuals.

    View details for Web of Science ID A1996UP10700002

    View details for PubMedID 8725996

  • Human CD4(+) and CD8(+) T lymphocytes are both cytotoxic to Toxoplasma gondii-infected cells INFECTION AND IMMUNITY Montoya, J. G., Lowe, K. E., CLAYBERGER, C., Moody, D., Do, D., Remington, J. S., Talib, S., Subauste, C. S. 1996; 64 (1): 176-181

    Abstract

    Studies to determine if Toxoplasma gondii-specific human T cells lyse parasite-infected cells have yielded conflicting results. Furthermore, attempts to obtain human cytotoxic CD8+ T lymphocytes have been difficult because of the lack of a reproducible system for their generation. By using paraformaldehyde-fixed, T. gondii-infected peripheral blood mononuclear cells as antigen-presenting cells, we developed a method whereby T. gondii-specific T-cell lines can be reproducibly generated. Six T. gondii-specific T-cell lines were generated from an individual chronically infected with T. gondii. Cytofluorometric analysis of these lines revealed > 99% CD3+, 85 to 95% CD3+ alpha beta T-cell-receptor-positive (TCR+), 5 to 9% CD3+ gamma delta TCR+, 50 to 70% CD4+, and 20 to 40% CD8+ cells when cells were examined during the first 3 weeks of stimulation and >99% CD3+, >99% CD3+ alpha beta TCR+, < 1% CD3+ gamma delta TCR+, 20 to 40% CD4+, and 60 to 80% CD8+ cells when cells were examined between 5 and 11 weeks. Both CD4+ and CD8+ T cells had remarkable cytotoxic activity against T. gondii-infected target cells (30 to 50% specific Cr release at an effector-to-target ratio of 30:1) but not against uninfected target cells ( < 10% at an effector-to-target ratio of 30:1). Cytotoxic activity by the whole T-cell lines was not T. gondii strain specific. Whole T-cell lines were cytotoxic for target cells infected with the C56 and ME49 strains and the RH strain (which was used to infect peripheral blood mononuclear cells). T. gondii-specific T-cell lines displayed the predominant expression of V beta 7 TCR. The CDR3 regions of the V beta 7 TCRs of these T-cell lines showed a striking degree of sequence identity (oligoclonality). T-cell lines obtained by the method reporter here can be used to characterize functional activity of T-lymphocyte subsets in humans infected with T. gondii.

    View details for Web of Science ID A1996TM71800025

    View details for PubMedID 8557337

  • Cells and cytokines in resistance to Toxoplasma gondii TOXOPLASMA GONDII Hunter, C. A., Suzuki, Y., Subauste, C. S., Remington, J. S. 1996; 219: 113-125

    View details for Web of Science ID A1996BJ59J00011

    View details for PubMedID 8791694

  • The role of IL12 in toxoplasmosis RESEARCH IN IMMUNOLOGY Hunter, C. A., Remington, J. S. 1995; 146 (7-8): 546-551

    View details for Web of Science ID A1995TW31300076

    View details for PubMedID 8839160

  • DEFINITIVE IDENTIFICATION OF A GENE THAT CONFERS RESISTANCE AGAINST TOXOPLASMA CYST BURDEN AND ENCEPHALITIS IMMUNOLOGY Brown, C. R., Hunter, C. A., Estes, R. G., Beckmann, E., Forman, J., David, C., Remington, J. S., McLeod, R. 1995; 85 (3): 419-428

    Abstract

    Control of resistance to cyst burden following per-oral infection with Toxoplasma gondii has been mapped previously to a region of mouse chromosome 17 of approximately 140 kb. This region is contiguous with and contains the class I gene, Ld. Resistance to development of toxoplasmic encephalitis has also been reported to be controlled by genes in this region of H-2. TNF-alpha, D and L genes, as well as unidentified genes, are also in this region. The work described here was performed to identify definitively the gene(s) in this 140 kb region that confers resistance to cysts and encephalitis. The study demonstrates that relative resistance to T. gondii organisms and cyst burden in brain, and toxoplasmic encephalitis, 30 days following per-oral T. gondii infection is correlated absolutely with the presence of the Ld gene in inbred, recombinant, mutant and C3H.Ld transgenic mice. Mice with the Ld gene had lower cyst burdens and less encephalitis than those without the Ld gene. Specifically, 30 days after infection mice with the Ld gene had minimal perivascular inflammation and meningeal inflammation and very few Toxoplasma cysts or organisms in immunoperoxidase-stained preparations of their brains. Mice without the Ld gene had a similar pattern of inflammation, but in addition they had collections of inflammatory cells in the brain parenchyma. Free tachyzoites were found within these foci of inflammation and cysts were present in these areas as well as in contiguous areas without inflammatory cells. There were CD4+ and CD8+ T lymphocytes in the areas of inflammation and throughout the brain parenchyma. Mice that were resistant to cysts and encephalitis had little detectable brain cytokine mRNA expression, while mice that were susceptible had elevated levels of mRNA for a wide range of cytokines, consistent with their greater amounts of inflammation. The present work definitively demonstrates that a Ld-restricted response decreases the number of organisms and cysts within the brain and thereby limits toxoplasmic encephalitis and levels of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10, transforming growth factor-beta (TGF-beta), IL-1 alpha, IL1 beta and macrophage inhibiting protein (MIP) mRNA in the brain 30 days after per-oral infection.

    View details for Web of Science ID A1995RK30100011

    View details for PubMedID 7558130

  • PREFERENTIAL ACTIVATION AND EXPANSION OF HUMAN PERIPHERAL-BLOOD GAMMA-DELTA T-CELLS IN RESPONSE TO TOXOPLASMA GONDII IN VITRO AND THEIR CYTOKINE PRODUCTION AND CYTOTOXIC ACTIVITY AGAINST T-GONDII-INFECTED CELLS JOURNAL OF CLINICAL INVESTIGATION Subauste, C. S., Chung, J. Y., Do, D., Koniaris, A. H., Hunter, C. A., Montoya, J. G., Porcelli, S., Remington, J. S. 1995; 96 (1): 610-619

    Abstract

    Studies were conducted to determine if gamma delta T cells participate in the immune response to Toxoplasma gondii. Preferential expansion of human gamma delta T cells occurred when peripheral blood T cells from either T. gondii-seronegative or seropositive individuals were incubated with autologous PBMC infected with the parasite. That gamma delta T cells proliferated after incubation with infected cells was confirmed using purified of gamma delta T cells. These T. gondii-induced gamma delta T cell responses did not require prior exposure to the parasite since T cells obtained from umbilical cord blood from seronegative newborns also exhibited preferential expansion of gamma delta T cells. Cytofluorometric analysis of T cells obtained from either umbilical cord blood or peripheral blood from adults revealed that V gamma 9+ and V delta 2+ gamma delta T cells responded to stimulation with infected cells. Preferential expansion of gamma delta T cells was not restricted by polymorphic determinants of MHC molecules. PBMC that had internalized killed parasites but not PBMC incubated with T. gondii lysate antigens also stimulated preferential expansion and activation of gamma delta T cells as assessed by expression of CD25 and HLA-DR molecules. V gamma 9+V delta 2+ gamma delta T cells were cytotoxic for T. gondii-infected cells in an MHC-unrestricted manner, and produced IFN-gamma, IL-2, TNF-alpha, but not IL-4 when incubated with cells infected with the parasite. These results suggest that rapid induction of a remarkable primary gamma delta T cell response may be important in the early protective immune response to T. gondii.

    View details for Web of Science ID A1995RH89400073

    View details for PubMedID 7615835

  • IL-1b is required for IL-12 to induce production of IFN-j by NK cells. J. Immun. Remington J.S., Hunter C.A., Chizzonite R. 1995: 4347-4354
  • Transforming growth factor-b inhibits interleukin-12 induced production of interferon-g by natural killer cells: a role for transforming growth factor-b in the regulation of T cell-independent resistance to Toxoplasma gondii. Eur. J. Immun. Remington J.S., Hunter C.A., Bermudez L.E., Beernink H., Waegell W. 1995: 994-1000
  • IMMUNOCYTOCHEMICAL DETECTION OF CYTOKINES IN THE LYMPH-NODES AND BRAINS OF MICE RESISTANT OR SUSCEPTIBLE TO TOXOPLASMIC ENCEPHALITIS JOURNAL OF INFECTIOUS DISEASES Hunter, C. A., Litton, M. J., Remington, J. S., Abrams, J. S. 1994; 170 (4): 939-945

    Abstract

    BALB/c mice develop toxoplasmic encephalitis (TE) but the pathology resolves; in contrast, CBA/Ca mice develop progressive TE. Immunohistochemical analysis revealed peak staining for interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) in lymph nodes of both strains on day 7 of infection, with elevated levels of IFN-gamma and TNF persisting in CBA/Ca mice. TNF was present in the central nervous systems (CNS) of both strains of mice and correlated with severity of pathology. Interleukin (IL)-2 was detected in lymph nodes and CNS of CBA/Ca mice after day 52 of infection and only in the lymph nodes of BALB/c mice between days 14 and 21 after infection. Highest levels of IL-10 were observed in lymph nodes and CNS of infected CBA/Ca mice. Variations in cytokine levels in lymph nodes and CNS of these mouse strains may account for differences in their susceptibility to TE.

    View details for Web of Science ID A1994PJ69400029

    View details for PubMedID 7930739

  • TOXOPLASMOSIS IN PREGNANCY CLINICAL INFECTIOUS DISEASES Wong, S. Y., Remington, J. S. 1994; 18 (6): 853-861

    View details for Web of Science ID A1994NQ82600001

    View details for PubMedID 8086543

  • Toxoplasma-macrophage interactions. Immunology series Beaman, M. H., Subauste, C. S., Wong, S. Y., Remington, J. S. 1994; 60: 475-493

    View details for PubMedID 8251588

  • THE ROLE OF CYTOKINES IN TOXOPLASMOSIS BIOTHERAPY Hunter, C. A., Subauste, C. S., Remington, J. S. 1994; 7 (3-4): 237-247

    Abstract

    Infection with Toxoplasma gondii is normally asymptomatic, but as a consequence of the AIDS epidemic the incidence of symptomatic disease and especially toxoplasmic encephalitis (TE) has grown in frequency. The high frequency of adverse reactions to conventional therapeutic regimens for toxoplasmosis highlight the need to develop new strategies for the management of this disease. The importance of cytokines in resistance against T. gondii has been shown primarily in murine models of toxoplasmosis and a number of cytokines (e.g., IFN-gamma, TNF-alpha, IL-2 and IL-12) have been proposed for trials in patients with TE. One mechanism by which these cytokines produce their effects is through stimulation of macrophages and/or NK cells. However, there are problems with immunological intervention in immunocompromised patients with TE since the infection is present primarily in the central nervous system (CNS), an immunoprivileged site, and because certain cytokines may down regulate the immune response. While much valuable information has been obtained from studies conducted in immunocompetent strains of mice their relevance to an immunocompromised host is unknown. The development of genetically altered mice with immune deficiencies offers promising new models that may allow for more rational development of new treatment regimens.

    View details for Web of Science ID A1994PQ40500010

    View details for PubMedID 7865354

  • TOXOPLASMOSIS IN PATIENTS WITH CANCER CLINICAL INFECTIOUS DISEASES Israelski, D. M., Remington, J. S. 1993; 17: S423-S435

    Abstract

    The unusual occurrence, protein manifestations, and often devastating consequences of toxoplasmosis in patients with cancer emphasize the need for clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis in patients with cancer has most commonly been described in association with Hodgkin's disease. It has also been reported, usually in the setting of treatment with antineoplastic agents, in patients with other lymphoproliferative disorders, hematologic malignancies, and solid tumors. In this review, among patients for whom the diagnosis was made early enough to begin specific treatment, conditions of 68% improved; this finding was in marked contrast to the severe morbidity and mortality observed for untreated individuals. The high mortality in the untreated group reflects the general debilitation and severe immunocompromise of these patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it was not necessarily always the proximate cause of death.

    View details for Web of Science ID A1993MF18700022

    View details for PubMedID 8274608

  • CYTOKINE MESSENGER-RNA IN THE CENTRAL-NERVOUS-SYSTEM OF SCID MICE INFECTED WITH TOXOPLASMA-GONDII - IMPORTANCE OF T-CELL-INDEPENDENT REGULATION OF RESISTANCE TO TOXOPLASMA-GONDII INFECTION AND IMMUNITY Hunter, C. A., Abrams, J. S., Beaman, M. H., Remington, J. S. 1993; 61 (10): 4038-4044

    Abstract

    Levels of cytokine mRNA were studied in the central nervous system (CNS) of SCID mice infected with Toxoplasma gondii. This infection led to 100% mortality by day 23 postinfection. Inflammation was observed in the lungs on day 7 and in the heart, liver, and kidneys on days 14 and 18 of infection. In the CNS, necrotic, acellular lesions that contained numerous parasites, accompanied by a localized astrocyte activation, were evident on day 14. Polymerase chain reaction-assisted amplification of RNA revealed that, although transcripts for interleukin-1 alpha (IL-1 alpha) and IL-1 beta were present in the brains of uninfected mice, increased levels of these transcripts were detected on day 7 of infection. Transcripts for macrophage inflammatory protein 1 and transforming growth factor beta were also detected in brains of infected mice at this time point. On days 14 and 18, levels of these transcripts had increased and transcripts for IL-6, IL-10, gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were also detected. Transcripts for IL-2 or IL-4 were not detected at any of the time points. Detection of locally produced cytokine transcripts may reflect involvement of the cytokines in the immunopathogenesis of this infection or involvement in mediating antitoxoplasma activity. To assess the possible role of endogenous IFN-gamma, TNF-alpha, IL-10, IL-6, and GM-CSF, cytokine-neutralizing monoclonal antibodies were administered to infected SCID mice. Neutralization of IFN-gamma or TNF-alpha led to earlier mortality than that in controls. In contrast, treatment with antibody to IL-10 and IL-6 increased survival time. Treatment with anti-GM-CSF did not alter the time to death. These results indicate that TNF-alpha and IFN-gamma are both involved in T-cell-independent mechanisms of resistance to T. gondii in SCID mice and that IL-10 and IL-6 may downregulate the immune response to this pathogen.

    View details for Web of Science ID A1993LZ26400003

    View details for PubMedID 8406791

  • IMMUNITY TO TOXOPLASMA-GONDII CURRENT OPINION IN IMMUNOLOGY Subauste, C. S., Remington, J. S. 1993; 5 (4): 532-537

    Abstract

    Recent advances in our understanding of the immunological mechanisms involved during infection with Toxoplasma gondii include evidence for the role of different subsets of lymphocytes and cytokines in acute infection as well as in reactivation of chronic infection. The mechanisms of presentation of T. gondii antigen have been clarified recently, and animal models of toxoplasmosis that mimic disease observed in AIDS patients developed.

    View details for Web of Science ID A1993LU97500010

    View details for PubMedID 8216929

  • PREVALENCE OF TOXOPLASMA INFECTION IN A COHORT OF HOMOSEXUAL MEN AT RISK OF AIDS AND TOXOPLASMIC ENCEPHALITIS JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Israelski, D. M., Chmiel, J. S., POGGENSEE, L., Phair, J. P., Remington, J. S. 1993; 6 (4): 414-418

    Abstract

    The purpose of this study was to characterize the epidemiologic, clinical, and laboratory parameters of a cohort of men at risk of AIDS-associated toxoplasmic encephalitis. One hundred seventeen (11%) of the 1,073 participants at the time of enrollment into the Chicago Multicenter AIDS Cohort Study (MACS) were seropositive for Toxoplasma antibodies. Significant differences in prevalence of antibodies between African-American, Hispanic, or white men were not observed (p = 0.49). One hundred one (86%) of the 117 antibody-positive participants had at least one follow-up serology performed and 6 (6%) of the 101 had a significant rise in IgG antibody titer on subsequent visits. Five of six participants with a significant rise in titer were also seropositive for HIV-1 at entry or seroconverted during the study. A trend toward higher IgG Toxoplasma titers and prevalence of IgM antibodies in participants seropositive for HIV-1 was observed, but the differences did not reach statistical significance. There was no evidence that the presence of Toxoplasma infection predisposed to development of CD4+ depletion or AIDS. None of the 183 individuals in the cohort who developed AIDS and who were seronegative for Toxoplasma antibodies developed toxoplasmic encephalitis. In contrast, of the 13 persons who developed AIDS and who were positive for Toxoplasma antibodies, 5 (38%) developed toxoplasmic encephalitis. Prevalence of Toxoplasma antibodies in the MACS population was independent of HIV-1 serostatus. Toxoplasma infection does not appear to predispose to progression of HIV-1 infection. The risk of development of toxoplasmic encephalitis in persons with AIDS and chronic Toxoplasma infection may have been underestimated by previous retrospective studies.

    View details for Web of Science ID A1993KU22100015

    View details for PubMedID 8455146

  • VACCINATION OF MICE WITH THE PROTECTIVE F3G3 ANTIGEN OF TOXOPLASMA-GONDII ACTIVATES CD4+ BUT NOT CD8+ T-CELLS AND INDUCES TOXOPLASMA SPECIFIC IGG ANTIBODY MOLECULAR IMMUNOLOGY Brinkmann, V., Remington, J. S., Sharma, S. D. 1993; 30 (4): 353-358

    Abstract

    A major cytoplasmic Toxoplasma gondii (T. gondii) antigen recognized by monoclonal antibody F3G3 (F3G3-Ag), as well as two surface antigens recognized by monoclonal antibodies 2G11 and 1E11 respectively (2G11-Ag; 1E11-Ag), were isolated from crude Toxoplasma sonicates using affinity chromatography. Purified F3G3-Ag induced long term protection against Toxoplasma infection in mice and induced Toxoplasma specific IgG antibody. CD4+ but not CD8+ T cells from immune animals proliferated and produced IL-2 upon restimulation with either Toxoplasma sonicate or F3G3-Ag in vitro. Furthermore, CD4+ T cells from mice immunized with F3G3-Ag responded to purified 2G11- and 1E11-Ag. In contrast, CD4+ T cells from mice immunized with 2G11-Ag responded to Toxoplasma sonicate and 2G11-Ag, but not to F3G3- or 1E11-Ag. The results may indicate that the protective F3G3-Ag shares immunogenic epitopes present also on 2G11- and 1E11-Ag, since the F3G3-Ag used for the vaccination did not contain detectable amounts of 2G11- or 1E11-Ag, and none of the antigens displayed any mitogenicity. Taken together the results show that the cytoplasmic F3G3-Ag of T. gondii induces CD4+ T helper cells, Toxoplasma specific IgG antibodies and long term protection against Toxoplasma infection, but does not induce detectable sensitization of the CD8+ T cell compartment.

    View details for Web of Science ID A1993KT20300003

    View details for PubMedID 8096062

  • THE ACTIVITY OF ATOVAQUONE-(566C80) IN MURINE TOXOPLASMOSIS IS MARKEDLY AUGMENTED WHEN USED IN COMBINATION WITH PYRIMETHAMINE OR SULFADIAZINE JOURNAL OF INFECTIOUS DISEASES Araujo, F. G., Lin, T., Remington, J. S. 1993; 167 (2): 494-497

    Abstract

    The activity of atovaquone in the treatment of murine toxoplasmosis was greatly enhanced when administered in combination with pyrimethamine or sulfadiazine. Mice infected with lethal inocula of tachyzoites or cysts of Toxoplasma gondii and treated with doses of atovaquone, pyrimethamine, or sulfadiazine that were ineffective when administered alone had 70% survival when pyrimethamine plus atovaquone and 100% survival when sulfadiazine plus atovaquone was used. Of interest, doses of pyrimethamine and, particularly, sulfadiazine far below the doses that would induce any protection in infected mice were active when combined with atovaquone. These results suggest that clinical trials for treatment of toxoplasmosis in AIDS patients using the combination of atovaquone with sulfadiazine or pyrimethamine are justified.

    View details for Web of Science ID A1993KJ48700040

    View details for PubMedID 8421189

  • Toxoplasmosis in the non-AIDS immunocompromised host. Current clinical topics in infectious diseases Israelski, D. M., Remington, J. S. 1993; 13: 322-356

    View details for PubMedID 8397917

  • CYTOKINES, TOXOPLASMA AND INTRACELLULAR PARASITISM IMMUNOLOGICAL REVIEWS Beaman, M. H., Wong, S. Y., Remington, J. S. 1992; 127: 97-117

    View details for Web of Science ID A1992JD81800005

    View details for PubMedID 1506009

  • MURINE CD8+ CYTOTOXIC LYMPHOCYTES-T LYSE TOXOPLASMA-GONDII-INFECTED CELLS JOURNAL OF IMMUNOLOGY Subauste, C. S., Koniaris, A. H., Remington, J. S. 1991; 147 (11): 3955-3959

    Abstract

    Studies were performed to determine whether CTL against Toxoplasma gondii-infected cells could be induced in a murine model of T. gondii infection in which CD8+ T lymphocytes have been shown to play a major role in resistance against this parasite. In 51Cr release assays, nylon wool nonadherent spleen cells from BALB/c (H-2d) mice immunized with the temperature-sensitive (ts-4) mutant strain of T. gondii were cytotoxic for T. gondii-infected P815 (H-2d) mastocytoma cells but not for uninfected cells. This cytotoxic activity was remarkably increased after in vitro stimulation with T. gondii-infected syngeneic spleen cells. The effector cells were shown to be CD8+ T lymphocytes, because the cytotoxicity was significantly inhibited by depletion of CD8+ T lymphocytes but not by depletion of CD4+ T lymphocytes. This cytotoxic activity was genetically restricted. Spleen cells from T. gondii-immune BALB/c mice were not cytotoxic for T. gondii-infected EL4 (H-2b) thymoma cells, whereas spleen cells from T. gondii-immune C57B1/6 (H-2b) mice were cytotoxic for T. gondii-infected EL4 cells but not for T. gondii-infected P815 cells. The cytolytic activity of CD8+ T lymphocytes against T. gondii-infected cells might be a mechanism whereby these cells confer resistance against T. gondii.

    View details for Web of Science ID A1991GQ83700041

    View details for PubMedID 1940378

  • RAPID PRENATAL-DIAGNOSIS OF CONGENITAL TOXOPLASMA INFECTION BY USING POLYMERASE CHAIN-REACTION AND AMNIOTIC-FLUID JOURNAL OF CLINICAL MICROBIOLOGY GROVER, C. M., Thulliez, P., Remington, J. S., Boothroyd, J. C. 1990; 28 (10): 2297-2301

    Abstract

    Infection of pregnant women with Toxoplasma gondii places the developing fetus at risk for congenital infection. We report a prospective study of 43 documented cases of acute maternal Toxoplasma infections acquired during gestation in which the polymerase chain reaction (PCR) was evaluated for diagnosis of fetal infection and compared with the current standard methods. On the basis of direct lysis of pelleted amniotic fluid cells followed by amplification of a gene sequence specific for T. gondii, PCR correctly identified the presence of T. gondii in five of five samples of amniotic fluid from four proven cases of congenital infection. PCR also detected three of five positive cases from a nonprospective group. The two diagnostic methods of comparable speed, detection of specific immunoglobulin M from fetal blood and and inoculation of amniotic fluid into tissue culture, correctly identified only 3 and 4 of the 10 positive samples, respectively. The considerably more time-consuming methods of mouse inoculation of amniotic fluid and fetal blood both detected 7 of 10 positive samples. There were no false-positive diagnoses by any of the methods. Therefore, detection of T. gondii by PCR appears to be the most promising method for prenatal diagnosis of congenital Toxoplasma infection, since it is both extremely rapid and highly sensitive.

    View details for Web of Science ID A1990DZ42500028

    View details for PubMedID 2229355

  • THE TRAGEDY OF TOXOPLASMOSIS SYMP ON PERINATAL INFECTIOUS DISEASES : UPDATE 1990 Remington, J. S. LIPPINCOTT WILLIAMS & WILKINS. 1990: 762–63

    View details for Web of Science ID A1990EC31500022

    View details for PubMedID 2235157

  • TOXOPLASMIC ENCEPHALITIS IN AIDS HOSPITAL PRACTICE DANNEMANN, B. R., Remington, J. S. 1989; 24 (3): 139-?

    View details for Web of Science ID A1989T757700015

    View details for PubMedID 2493464

  • TREATMENT OF TOXOPLASMIC ENCEPHALITIS WITH INTRAVENOUS CLINDAMYCIN ARCHIVES OF INTERNAL MEDICINE DANNEMANN, B. R., Israelski, D. M., Remington, J. S. 1988; 148 (11): 2477-2482

    Abstract

    At present, therapy for toxoplasmic encephalitis (TE) is the combination of pyrimethamine with sulfadiazine or trisulfapyrimidines. Unfortunately, due to adverse reactions to sulfonamides, many patients with acquired immunodeficiency syndrome (AIDS) are unable to receive a complete course of therapy. The promising results with clindamycin phosphate therapy in a mouse model of TE prompted us to seek further information about patients with AIDS with TE who had been treated with clindamycin. Fifteen such patients were identified in whom clindamycin was used to treat 18 episodes of TE. Eleven patients showed clinical or radiologic improvement after receiving clindamycin therapy, either alone or in combination with pyrimethamine. Twelve received oral clindamycin as suppressive therapy after discharge from the hospital. Adverse reactions possibly related to clindamycin therapy included diarrhea, reversible granulocytopenia, and skin reactions. The results of this retrospective study suggest that clindamycin, either alone or in combination with pyrimethamine, may represent an effective alternative therapy for TE in patients with AIDS. Whether this supposition can be substantiated by appropriately designed studies is presently being determined.

    View details for Web of Science ID A1988Q934000022

    View details for PubMedID 3190380