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Luiz Ricardo Goulart - One of the best experts on this subject based on the ideXlab platform.

  • dIfferentIal expressIon of Ifn γ Il 10 tlr1 and tlr2 and theIr potentIal effects on downgradIng leprosy reactIon and erythema nodosum leprosum
    Clinical & Developmental Immunology, 2019
    Co-Authors: Douglas Eulalio Antunes, Luiz Ricardo Goulart, Isabela Maria Bernardes Goulart, Mayara Ingrid Sousa Lima, Patricia Terra Alves, Paula Cristina Brigido Tavares
    Abstract:

    Leprosy reactIons are acute ImmunologIcal events that occur durIng the evolutIon of chronIc InfectIous dIsease causIng neural damage and dIsabIlItIes. A study usIng blood samples of 17 leprosy reactIon patIents and 17 reactIon-free was carrIed out by means of assocIatIons between antIgens, receptors, and expressIon of cytokInes, usIng path analysIs provIdIng new InsIghts Into the ImmunologIcal mechanIsms Involved In trIggerIng leprosy reactIons. Toll-lIke receptors (TLR) such as TLR1 and TLR2, presented balanced expressIon In the reactIon-free multIbacIllary (MB) group (TLR1: 1.01 ± 0.23, TLR2: 1.22 ± 0.18; p = 0.267). On the other hand, downgradIng type 1 reactIon (T1R) (TLR1: 1.24 ± 0.17, TLR2: 2.88 ± 0.37; p = 0.002) and erythema nodosum leprosum (ENL) (TLR1: 1.93 ± 0.17, TLR2: 2.81 ± 0.15; p = 0.004) revealed an unbalance In relatIon to the expressIon of these receptors. When the path analysIs was approached, It was noted that InterleukIn 10 (IL-10) expressIon showed a dependence relatIon wIth PhenolIc GlycolIpId I (PGL-I) In downgradIng T1R (dIrect effect = 0.503 > resIdual effect = 0.364), whereas In ENL, such relatIonshIp occurred wIth lIpoarabInomannan (LAM) (dIrect effect = 0.778 > resIdual effect = 0.280). On the contrary, In the reactIon-free leprosy group, Interferon-gamma (IFN-γ) levels were dependent on the assocIatIon between TLR2 and TLR1 (0.8735). The hIgh TLR2 expressIon assocIated wIth IL-10 levels, In the leprosy reactIon groups, may be hypothetIcally related to the formatIon of TLR2/2 homodImers and/or TLR2/6 heterodImers lInked to evasIon mechanIsms In downgradIng reactIons and pathophysIology of ENL.

  • rIsk benefIt assessment of bacIllus calmette guerIn vaccInatIon antI PhenolIc GlycolIpId I serology and mItsuda test response 10 year follow up of household contacts of leprosy patIents
    Revista Da Sociedade Brasileira De Medicina Tropical, 2015
    Co-Authors: Sergio Eduardo Alonso Araujo, Luiz Ricardo Goulart, Diogo Carrijo Rodrigues De ,sousa, Marina Monteiro Figueiredo Rezende, Maraisa Resende Rosa, Danielle Cristina Dos Santos, Isabela Maria Bernardes Goulart
    Abstract:

    INTRODUCTION: DespIte multIdrug therapy, leprosy remaIns a publIc health Issue. The Intradermal BacIllus Calmette-GuerIn (BCG) vaccIne, MItsuda test (lepromIn skIn test), and antI-PhenolIc GlycolIpId I (PGL-I) serology are wIdely used In leprosy studIes and have shown great epIdemIologIcal value. METHODS: ThIs longItudInal study evaluated the relatIve rIsks and benefIts of these three tools by comparIng results observed In household contacts (HHCs) of leprosy patIents who developed leprosy wIth those of HHCs who dId not In a populatIon of 2,992 IndIvIduals monItored durIng a 10-year perIod. RESULTS : Seventy-fIve (2.5%) new leprosy cases were dIagnosed, IncludIng 28 (0.9%) co-prevalent cases. Therefore, for the rIsk-benefIt assessment, 47 (1.6%) HHCs were consIdered as truly dIagnosed durIng follow-up. The comparIson between healthy and affected contacts demonstrated that not only dId BCG vaccInatIon Increase protectIon, but boosters also Increased to 95% relatIve rIsk (RR) reductIon when results for havIng two or more scars were compared wIth havIng no scars [RR, 0.0459; 95% confIdence Interval (CI), 0.006-0.338]. SImIlarly, MItsuda reactIons >7mm In InduratIon presented 7-fold greater protectIon agaInst dIsease development compared to reactIons of 0-3mm (RR, 0.1446; 95% CI, 0.0566-0.3696). In contrast, antI-PGL-I ELISA seroposItIvIty IndIcated a 5-fold RR Increase for dIsease outcome (RR, 5.688; 95% CI, 3.2412-9.9824). The combIned effect of no BCG scars, MItsuda reactIon of <7mm, and seroposItIvIty to antI-PGL-I Increased the rIsk for leprosy onset 8-fold (RR, 8.109; 95% CI, 5.1167-12.8511). CONCLUSIONS: The adoptIon of these combIned assays may Impose measures for leprosy control strategIes.

  • UnveIlIng healthy carrIers and subclInIcal InfectIons among household contacts of leprosy patIents who play potentIal roles In the dIsease chaIn of transmIssIon
    Memórias do Instituto Oswaldo Cruz, 2012
    Co-Authors: Sergio Eduardo Alonso Araujo, Luiz Ricardo Goulart, Janaína Lobato, Érica De Melo Reis, Dulcinéa De Oliveira Bernardes De Souza, Maria Aparecida Gonçalves, Adeilson Vieira Da Costa, Isabela Maria Bernardes Goulart
    Abstract:

    Leprosy transmIssIon stIll occurs despIte the avaIlabIlIty of hIghly effectIve treatment. The next step towards successfully elImInatIng leprosy Is InterruptIng the chaIn of transmIssIon of the aetIologIcal agent, MycobacterIum leprae. In thIs InvestIgatIon, we provIde evIdence that household contacts (HHCs) of leprosy patIents mIght not only have subclInIcal InfectIons, but may also be actIvely Involved In bacIllI transmIssIon. We studIed 444 patIents and 1,352 contacts usIng antI-PhenolIc GlycolIpId-I (PGL-I) serology and quantItatIve polymerase chaIn reactIon (qPCR) to test for M. leprae DNA In nasal swabs. We classIfIed the patIents accordIng to the clInIcal form of theIr dIsease and the contacts accordIng to the characterIstIcs of theIr Index case. Overall, 63.3% and 34.2% of patIents tested posItIve by ELISA and PCR, respectIvely. For HHCs, 13.3% had a posItIve ELISA test result and 4.7% had a posItIve PCR test result. The presence of cIrculatIng antI-PGL-I among healthy contacts (wIth or wIthout a posItIve PCR test result from nasal swabs) was consIdered to IndIcate a subclInIcal InfectIon. DNA detected In nasal swabs also IndIcates the presence of bacIllI at the sIte of transmIssIon and bacterIal entrance. We suggest that the concomItant use of both assays may allow us to detect subclInIcal InfectIon In HHCs and to IdentIfy possIble bacIllI carrIers who may transmIt and dIssemInate dIsease In endemIc regIons. ChemoprophylaxIs of these contacts Is suggested.

P R Klatser - One of the best experts on this subject based on the ideXlab platform.

  • sImple and fast lateral flow test for classIfIcatIon of leprosy patIents and IdentIfIcatIon of contacts wIth hIgh rIsk of developIng leprosy
    Journal of Clinical Microbiology, 2003
    Co-Authors: Samira Buhrersekula, Henk L Smits, George C Gussenhoven, J Van Leeuwen, S Amador, T Fujiwara, P R Klatser, Linda Oskam
    Abstract:

    The InterruptIon of leprosy transmIssIon Is one of the maIn challenges for leprosy control programs sInce no consIstent evIdence exIsts that transmIssIon has been reduced after the IntroductIon of multIdrug therapy. Sources of InfectIon are prImarIly people wIth hIgh loads of bacterIa wIth or wIthout clInIcal sIgns of leprosy. The avaIlabIlIty of a sImple test system for the detectIon of antIbodIes to PhenolIc GlycolIpId-I (PGL-I) of MycobacterIum leprae to IdentIfy these IndIvIduals may be Important In the preventIon of transmIssIon. We have developed a lateral flow assay, the ML Flow test, for the detectIon of antIbodIes to PGL-I whIch takes only 10 mIn to perform. An agreement of 91% was observed between enzyme-lInked Immunosorbent assay and our test; the agreement beyond chance (kappa value) was 0.77. We evaluated the use of whole blood by comparIng 539 blood and serum samples from an area of hIgh endemIcIty. The observed agreement was 85.9% (kappa = 0.70). Storage of the lateral flow test and the runnIng buffer at 28°C for up to 1 year dId not Influence the results of the assay. The sensItIvIty of the ML Flow test In correctly classIfyIng MB patIents was 97.4%. The specIfIcIty of the ML Flow test, based on the results of the control group, was 90.2%. The ML Flow test Is a fast and easy-to-perform method for the detectIon of ImmunoglobulIn M antIbodIes to PGL-I of M. leprae. It does not requIre any specIal equIpment, and the hIghly stable reagents make the test robust and suItable for use In tropIcal countrIes.

  • A SIMPLE DIPSTICK ASSAY FOR THE DETECTION OF ANTIBODIES TO PhenolIc GlycolIpId-I OF MYCOBACTERIUM LEPRAE
    The American journal of tropical medicine and hygiene, 1998
    Co-Authors: S S Bührer, Henk L Smits, George C Gussenhoven, C. W. Van Ingen, P R Klatser
    Abstract:

    Among the many reported applIcatIons of the detectIon of antIbodIes to PhenolIc GlycolIpId-I (PGL-I) of MycobacterIum leprae, In partIcular, the use of seroprevalence as an IndIcator of the magnItude of the leprosy problem may turn out to be very useful In leprosy control programs. An operatIonal functIon of serology wIthIn the leprosy control servIces requIres a sImple test system. We have developed a sImple dIpstIck assay for the detectIon of antIbodIes to PGL-I and compared Its performance wIth that of an ELISA. A hIgh degree of agreement (97.2%) was observed between the ELISA and the dIpstIck assay when tested on 435 sera; the agreement beyond chance (Kappa value) was 0.92. No sIgnIfIcant dIfference was found between the dIpstIck assay and the ELISA when seroposItIvIty rates obtaIned In groups of leprosy patIents, household contacts, and controls were compared. The InterpretatIon of the dIpstIck results as posItIve or negatIve was unequIvocal, as Illustrated by the hIgh agreement between dIfferent persons readIng the test (Kappa values > 0.88). Storage of the only reagents requIred, the dIpstIcks and the stabIlIzed detectIon reagent, up to three weeks under tropIcal condItIons of hIgh temperatures, hIgh humIdIty, and exposure to lIght, dId not Influence the results of the assay. The dIpstIck assay descrIbed here Is an easy-to-perform method for the detectIon of IgM antIbodIes to PGL-I of M. leprae; It does not requIre any specIal equIpment and the hIghly stable reagents make the test robust and suItable for use In tropIcal countrIes. An Internal control valIdates the performance of the assay. ThIs dIpstIck assay may be the method of choIce for epIdemIologIc mappIng of leprosy.

  • follow up of multIbacIllary leprosy patIents usIng a PhenolIc GlycolIpId I based elIsa do IncreasIng elIsa values after dIscontInuatIon of treatment IndIcate relapse
    Leprosy Review, 1992
    Co-Authors: R A Chinalien, William R Faber, M M Van Rens, D L Leiker, Bernard Naafs, P R Klatser
    Abstract:

    WIth the IntroductIon of reproducIble serologIcal tests It was hoped that relapses In leprosy patIents, after dIscontInuIng treatment, could be detected before damagIng reactIons occurred and before the patIents became InfectIous. The possIble value of an ELISA usIng a semIsynthetIc analogue of PhenolIc GlycolIpId-I to detect antIbodIes to thIs antIgen In order to predIct a relapse In multIbacIllary patIents was InvestIgated. In contrast to that reported for paucIbacIllary patIents, thIs test was useful to detect early relapses In multIbacIllary patIents. In 3 out of 4 multIbacIllary patIents who relapsed, the ELISA-values were Increased. The decreased ELISA-values In the one relapsed patIent could be attrIbuted to the cortIcosteroId therapy. In the multIbacIllary patIents who dId not relapse after RFT, the ELISA-values were consIstently low or decreased. In only one patIent dId the ELISA-values Increase followIng hIs release from treatment and thIs patIent was clInIcally suspected of developIng a relapse.

Malcolm S Duthie - One of the best experts on this subject based on the ideXlab platform.

  • comparIson of enzyme lInked Immunosorbent assay usIng eIther natural octyl dIsaccharIde leprosy IdrI dIagnostIc or PhenolIc GlycolIpId I antIgens for the detectIon of leprosy patIents In colombIa
    American Journal of Tropical Medicine and Hygiene, 2017
    Co-Authors: Monica Munoz, Malcolm S Duthie, Juan Camilo Beltranalzate, Hector Serranocoll, Nora Cardonacastro
    Abstract:

    Abstract. Leprosy Is a chronIc InfectIous dIsease wIth a broad spectrum of manIfestatIons. Delays In attaInIng correct dIagnosIs permIt progressIve perIpheral nerve damage that can produce IrreversIble dIsabIlItIes. Tests detectIng antIgen-specIfIc antIbodIes can aId the dIagnostIc process and potentIally detect patIents earlIer. Reported tests have lacked optImal sensItIvIty and specIfIcIty; however, the need to develop new tests to aId early dIagnosIs stIll remaIns. In thIs study, we determIned the sensItIvIty, specIfIcIty, posItIve predIctIve value, and negatIve predIctIve value of enzyme-lInked Immunosorbent assay (ELISA) usIng natural octyl dIsaccharIde-leprosy IDRI dIagnostIc (NDO-LID). Serum samples from confIrmed multIbacIllary patIents (N = 338) and paucIbacIllary patIents (N = 58) were evaluated and contrasted agaInst samples from IndIvIduals wIthout leprosy (100 healthy persons, 36 leIshmanIasIs or tuberculosIs patIents). ELISA detectIng eIther antIgen-specIfIc IgM, IgG, or the combInatIon of IgG and IgM (wIth proteIn A) were conducted. At a sensItIvIty of 78% among all patIents, serum IgM antIbodIes agaInst the NDO-LID conjugate were detected at a greater level than those recognIzIng PhenolIc GlycolIpId-I antIgen (64% overall sensItIvIty), whIle provIdIng sImIlar specIfIcIty (97% versus 100%, respectIvely). GIven the InclusIon of the LID-1 proteIn wIthIn NDO-LID, we also detected conjugate-specIfIc IgG wIthIn patIent sera at a sensItIvIty of 81.6%. The use of proteIn A to sImultaneously detect both antIgen-specIfIc IgG and IgM Isotypes yIelded the hIghest overall sensItIvIty of 86.3%. Taken together, our data IndIcate that the detectIon of both IgG and IgM antIbodIes agaInst NDO-LID wIth proteIn A provIded the best overall abIlIty to detect ColombIan leprosy patIents.

  • IntegratIve lIterature revIew of the reported uses of serologIcal tests In leprosy management
    Sociedade Brasileira de Medicina Tropical (SBMT), 2016
    Co-Authors: Angelica Da Conceicao Oliveira Coelho Fabri, Ana Paula Mendes Carvalho, Malcolm S Duthie, Nayara Figueiredo Vieira, Isabela De Caux Bueno, Rayssa Nogueira Rodrigues, Thayenne Barrozo Mota Monteiro, Rodrigo Correa-oliveira, Francisco Carlos Felix Lana
    Abstract:

    Abstract: An IntegratIve lIterature revIew was conducted to synthesIze avaIlable publIcatIons regardIng the potentIal use of serologIcal tests In leprosy programs. We searched the databases LIteratura LatIno-AmerIcana e do CarIbe em CIêncIas da Saúde, ÍndIce BIblIográfIco Espanhol em CIêncIas da Saúde, Acervo da BIblIoteca da OrganIzação Pan-AmerIcana da Saúde, MedIcal LIterature AnalysIs and RetrIeval System OnlIne, Hanseníase, NatIonal LIbrary of MedIcIne, Scopus, OvId, CInahl, and Web of ScIence for artIcles InvestIgatIng the use of serologIcal tests for antIbodIes agaInst PhenolIc GlycolIpId-I (PGL-I), ML0405, ML2331, leprosy IDRI dIagnostIc-1 (LID-1), and natural dIsaccharIde octyl-leprosy IDRI dIagnostIc-1 (NDO-LID). From an InItIal pool of 3.514 artIcles, 40 full-length artIcles fulfIlled our InclusIon crIterIa. Based on these papers, we concluded that these antIbodIes can be used to assIst In dIagnosIng leprosy, detectIng neurItIs, monItorIng therapeutIc effIcacy, and monItorIng household contacts or at-rIsk populatIons In leprosy-endemIc areas. Thus, avaIlable data suggest that serologIcal tests could contrIbute substantIally to leprosy management

  • MultIbacIllary leprosy patIents wIth hIgh and persIstent serum antIbodIes to leprosy IDRI dIagnostIc-1/LID-1: hIgher susceptIbIlIty to develop type 2 reactIons
    Instituto Oswaldo Cruz Ministério da Saúde, 2015
    Co-Authors: Danielle De Freitas Mizoguti, Mauricio Barcelos Costa, Ana Lucia Maroclo Sousa, Malcolm S Duthie, Emerith Mayra Hungria, Aline Araújo Freitas, Regiane Morillas Oliveira, Ludimila Paula Vaz Cardoso, Mariane Martins Araújo Stefani
    Abstract:

    Leprosy Inflammatory epIsodes [type 1 (T1R) and type 2 (T2R) reactIons] represent the major cause of IrreversIble nerve damage. Leprosy serology Is known to be Influenced by the patIent’s bacterIal Index (BI) wIth hIgher posItIvIty In multIbacIllary patIents (MB) and specIfIc multIdrug therapy (MDT) reduces antIbody productIon. ThIs study evaluated by ELISA antIbody responses to leprosy InfectIous DIsease Research InstItute dIagnostIc-1 (LID-1) fusIon proteIn and PhenolIc GlycolIpId I (PGL-I) In 100 paIred serum samples of 50 MB patIents collected In the presence/absence of reactIons and In nonreactIonal patIents before/after MDT. PatIents who presented T2R had a medIan BI of 3+, whIle MB patIents wIth T1R and nonreactIonal patIents had medIan BI of 2.5+ (p > 0.05). AntI-LID-1 and antI-PGL-I antIbodIes declIned In patIents dIagnosed durIng T1R (p < 0.05). AntI-LID-1 levels waned In MB wIth T2R at dIagnosIs and nonreactIonal MB patIents (p < 0.05). HIgher antI-LID-1 levels were seen In patIents wIth T2R at dIagnosIs (vs. patIents wIth T1R at dIagnosIs, p = 0.008; vs. nonreactIonal patIents, p = 0.020) and In patIents wIth T2R durIng MDT (vs. nonreactIonal MB, p = 0.020). In MB patIents, hIgh and persIstent antI-LID-1 antIbody levels mIght be a useful tool for clInIcIans to predIct whIch patIents are more susceptIble to develop leprosy T2R

  • analysIs of antIbody responses to mycobacterIum leprae PhenolIc GlycolIpId I lIpoarabInomannan and recombInant proteIns to defIne dIsease subtype specIfIc antIgenIc profIles In leprosy
    Clinical and Vaccine Immunology, 2011
    Co-Authors: John S Spencer, Delphi Chatterjee, Robert H. Gelber, R. V. Cellona, Marivic F Balagon, Esterlina V Tan, Hee Jin Kim, William H Wheat, Paul Saunderson, Malcolm S Duthie
    Abstract:

    A sImple serodIagnostIc test based on the MycobacterIum leprae-specIfIc PhenolIc GlycolIpId I(PGL-I), for IndIvIduals wIth leprosy Is nearly unIversally posItIve In leprosy patIents wIth hIgh bacIllary loads but cannot be used as a stand-alone dIagnostIc test for the entIre spectrum of the dIsease process. For patIents wIth early InfectIon wIth no detectable acId-fast bacIllI In lesIons or wIth low or no antIbody tIter to PGL-I, as In those at the tuberculoId end of the dIsease spectrum, thIs dIagnostIc approach has lImIted usefulness. To IdentIfy addItIonal M. leprae antIgens that mIght enhance the serologIcal detectIon of these IndIvIduals, we have examIned the reactIvIty patterns of patIent sera to PGL-I, lIpoarabInomannan (LAM), and sIx recombInant M. leprae proteIns (ML1877, ML0841, ML2028, ML2038, ML0380, and ML0050) by Western blot analysIs and enzyme-lInked Immunosorbent assay (ELISA). Overall, the responses to ML2028 (Ag85B) and ML2038 (bacterIoferrItIn) were consIstently hIgh In both multIbacIllary and paucIbacIllary groups and weak or absent In endemIc controls, whIle responses to other antIgens showed consIderable varIabIlIty, from strongly posItIve to completely negatIve. ThIs analysIs has gIven a clearer understandIng of some of the dIfferences In the antIbody responses between IndIvIduals at opposIte ends of the dIsease spectrum, as well as IllustratIng the heterogeneIty of antIbody responses toward proteIn, carbohydrate, and GlycolIpId antIgens wIthIn a clInIcal group. CorrelatIng these response patterns wIth a partIcular dIsease state could allow for a more crItIcal assessment of the form of dIsease wIthIn the leprosy spectrum and could lead to better patIent management.

  • InsIght toward Early DIagnosIs of Leprosy through AnalysIs of the DevelopIng AntIbody Responses of
    2010
    Co-Authors: Mycobacterium Leprae-infected Armadillos, John S Spencer, Malcolm S Duthie, Richard W Truman, Wakako Goto, Marah N. Hay, Darrick Carter, Steven G. Reed
    Abstract:

    Leprosy Is a debIlItatIng chronIc dIsease caused by InfectIon wIth MycobacterIum leprae. A World Health OrganIzatIon-dIrected control strategy based upon the IdentIfIcatIon and treatment of patIents has resulted In a marked reductIon In the number of regIstered worldwIde leprosy cases over the last 20 years. DespIte these efforts, the number of new leprosy cases detected each year now remaIns relatIvely stable, and M. leprae InfectIon contInues to pose a health problem. It Is suggested that earlIer dIagnosIs Is requIred to strengthen control programs. In thIs study, we have examIned the development of antIgen-specIfIc ImmunoglobulIn responses wIthIn armadIllos experImentally Infected wIth M. leprae to IdentIfy those responses that develop most rapIdly and robustly followIng InfectIon. AntIbody responses to the M. leprae-specIfIc PhenolIc GlycolIpId I and several proteIn antIgens prevIously demonstrated to have dIagnostIc potentIal were assessed. Our results IdentIfy several antIgens that can provIde early dIagnosIs of M. leprae InfectIon but also IndIcate consIderable varIabIlIty In the development of antIgen-specIfIc antIbodIes. Our data suggest that a combInatIon of antIgens Is lIkely requIred to provIde accurate and early leprosy dIagnosIs. Leprosy Is caused by InfectIon wIth the bacterIum Mycobac-terIum leprae, and Its clInIcal symptoms, bacterIal burdens, pa-thology, and underlyIng ImmunologIcal responses vary wIdely

Linda Oskam - One of the best experts on this subject based on the ideXlab platform.

  • CumulatIve IncIdence of NFI for rIsk groups defIned by the adjusted predIctIon rule, usIng WHO leprosy classIfIcatIon and presence of antI-PGL-I antIbodIes as predIctIve varIables.
    2013
    Co-Authors: Ron P. Schuring, William R Faber, Jan H. Richardus, Ewout W. Steyerberg, David Pahan, Linda Oskam
    Abstract:

    NFI = nerve functIon ImpaIrment, PGL-I = PhenolIc GlycolIpId I.

  • the relatIon between seroprevalence of antIbodIes agaInst PhenolIc GlycolIpId I among school chIldren and leprosy endemIcIty In brazIl
    Revista Da Sociedade Brasileira De Medicina Tropical, 2008
    Co-Authors: Samira Buhrersekula, Linda Oskam, William R Faber, Stella M Van Beers, Rita Lecco, Elisabete Santos Madeira, Marco Antonio Lopes Dutra, Magali Chaves Luis, P R Klatser
    Abstract:

    Leprosy control programs would benefIt expressIvely from an easy method to estImate dIsease prevalence and to assess the effect of leprosy control measures on dIsease prevalence. DetermInatIon of the seroprevalence of antIbodIes to PGL-I through school chIldren surveys mIght be a useful IndIcator of leprosy prevalence at the dIstrIct level. To InvestIgate whether seroposItIvIty rates could be related to leprosy detectIon rates and whether seroposItIvIty could be used as a proxImal IndIcator to predIct the leprosy IncIdence In other areas, 7,073 school chIldren In three dIfferent leprosy-endemIc states In BrazIl were tested. The results show a wIdely varyIng dIstrIbutIon of seroposItIvIty In the communItIes Independent of the number of leprosy cases detected. Seroprevalence was sIgnIfIcantly lower at prIvate schools. No dIfferences In the patterns of seroposItIvIty between ELISA and dIpstIck were observed. No correlatIon between leprosy detectIon rate and seroposItIvIty rates could be establIshed.

  • the ml flow test as a poInt of care test for leprosy control programmes potentIal effects on classIfIcatIon of leprosy patIents
    Leprosy Review, 2007
    Co-Authors: Samira Buhrersekula, P R Klatser, Jan Visschedijk, Maria Aparecida De Faria Grossi, Krishna P Dhakal, Abdullahi U Namadi, Linda Oskam
    Abstract:

    OBJECTIVE: To evaluate the use of the ML Flow test as an addItIonal, serologIcal, tool for the classIfIcatIon of new leprosy patIents. DESIGN: In BrazIl, Nepal and NIgerIa, 2632 leprosy patIents were classIfIed by three METHODS: : (1) as multIbacIllary (MB) or paucIbacIllary (PB) accordIng to the number of skIn lesIons (WHO classIfIcatIon), (2) by slIt skIn smear examInatIon, and (3) by serology usIng the ML Flow test detectIng IgM antIbodIes to MycobacterIum leprae-specIfIc PhenolIc GlycolIpId-I. RESULTS: The proportIon of MB leprosy patIents was 39.5, 35.6 and 19.4% In BrazIl, Nepal and NIgerIa, respectIvely. The hIghest seroposItIvIty In patIents was observed In NIgerIa (62.9%), followed by BrazIl (50.8%) and Nepal (35.6%). ML Flow test results and smears were negatIve In 69.1 and 82.7% of PB patIents, whIle smears were posItIve In 58.6% of MB patIents In BrazIl and 28.3% In Nepal. In MB patIents, both smears and ML Flow tests were negatIve In 15.6% In BrazIl and 38.3%, In Nepal. TestIng all PB patIents wIth the ML Flow test to prevent under-treatment would Increase the MB group by 18, 11 and 46.2% for BrazIl, Nepal and NIgerIa, respectIvely. UsIng the ML Flow test as the sole crIterIon for classIfIcatIon would result In an Increase of 11.3 and 43.5% of patIents requIrIng treatment for MB leprosy In BrazIl and NIgerIa, respectIvely, and a decrease of 3.7% for Nepal. CONCLUSIONS: The ML Flow test could be used to strengthen classIfIcatIon, reduce the rIsk of under-treatment and mInImIze the need for slIt skIn smears.

  • hIgh prevalence of vasomotor reflex ImpaIrment In newly dIagnosed leprosy patIents
    European Journal of Clinical Investigation, 2005
    Co-Authors: Ximena Illarramendi, Samira Buhrersekula, Linda Oskam, A M Sales, M I Bakker, Ariane Leite De Oliveira, Jose Augusto Da Costa Nery, Annelies Wildersmith, Elizabeth P Sampaio, Euzenir Nunes Sarno
    Abstract:

    Background  InItIal nerve damage In leprosy occurs In small myelInated and unmyelInated nerve fIbers. Early detectIon of leprosy In the perIpheral nervous system Is challengIng as extensIve nerve damage may take place before clInIcal sIgns of leprosy become apparent. PatIents and methods  In order to determIne the prevalence of, and factors assocIated wIth, perIpheral autonomIc nerve dysfunctIon In newly dIagnosed leprosy patIents, 76 BrazIlIan patIents were evaluated prIor to treatment. SkIn vasomotor reflex was tested by means of laser Doppler velocImetry. Blood perfusIon and reflex vasoconstrIctIon followIng an InspIratory gasp were regIstered on the second and fIfth fIngers. Results  Vasomotor reflex was ImpaIred In at least one fInger In 33/76 (43%) patIents. The fIfth fIngers were more frequently ImpaIred and suffered more frequent bIlateral alteratIons than the second fIngers. MultIvarIate regressIon analysIs showed that leprosy reactIon (adjusted odds ratIo = 8·11, 95% confIdence Interval: 1·4–48·2) was assocIated wIth overall ImpaIred vasomotor reflex (average of the four fIngers). In addItIon, palmar erythrocyanosIs and an abnormal upper lImb sensory score were assocIated wIth vasomotor reflex ImpaIrment In the second fIngers, whereas antI-PhenolIc GlycolIpId-I antIbodIes, ulnar somatIc neuropathy and a low fInger skIn temperature were assocIated wIth ImpaIrment In the fIfth fIngers. ConclusIons  A hIgh prevalence of perIpheral autonomIc dysfunctIon as measured by laser Doppler velocImetry was observed In newly dIagnosed leprosy patIents, whIch Is clInIcally evIdent late In the dIsease. AutonomIc nerve lesIon was more frequent than somatIc lesIons and was strongly related to the Immune-Inflammatory reactIon agaInst M. leprae.

  • sImple and fast lateral flow test for classIfIcatIon of leprosy patIents and IdentIfIcatIon of contacts wIth hIgh rIsk of developIng leprosy
    Journal of Clinical Microbiology, 2003
    Co-Authors: Samira Buhrersekula, Henk L Smits, George C Gussenhoven, J Van Leeuwen, S Amador, T Fujiwara, P R Klatser, Linda Oskam
    Abstract:

    The InterruptIon of leprosy transmIssIon Is one of the maIn challenges for leprosy control programs sInce no consIstent evIdence exIsts that transmIssIon has been reduced after the IntroductIon of multIdrug therapy. Sources of InfectIon are prImarIly people wIth hIgh loads of bacterIa wIth or wIthout clInIcal sIgns of leprosy. The avaIlabIlIty of a sImple test system for the detectIon of antIbodIes to PhenolIc GlycolIpId-I (PGL-I) of MycobacterIum leprae to IdentIfy these IndIvIduals may be Important In the preventIon of transmIssIon. We have developed a lateral flow assay, the ML Flow test, for the detectIon of antIbodIes to PGL-I whIch takes only 10 mIn to perform. An agreement of 91% was observed between enzyme-lInked Immunosorbent assay and our test; the agreement beyond chance (kappa value) was 0.77. We evaluated the use of whole blood by comparIng 539 blood and serum samples from an area of hIgh endemIcIty. The observed agreement was 85.9% (kappa = 0.70). Storage of the lateral flow test and the runnIng buffer at 28°C for up to 1 year dId not Influence the results of the assay. The sensItIvIty of the ML Flow test In correctly classIfyIng MB patIents was 97.4%. The specIfIcIty of the ML Flow test, based on the results of the control group, was 90.2%. The ML Flow test Is a fast and easy-to-perform method for the detectIon of ImmunoglobulIn M antIbodIes to PGL-I of M. leprae. It does not requIre any specIal equIpment, and the hIghly stable reagents make the test robust and suItable for use In tropIcal countrIes.

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  • ComparIson of two rapId tests for antI-PhenolIc GlycolIpId-I serology In BrazIl and Nepal
    Memórias do Instituto Oswaldo Cruz, 2012
    Co-Authors: Mariane Martins De Araujo Stefani, Mauricio Barcelos Costa, Adriano Badotti Grassi, Lucas H. Sampaio, Ana Lucia Maroclo Sousa, Pauline Scheelbeek, Kapil D. Neupane, Deanna A. Hagge, Murdo Macdonald, Sang Nae Cho
    Abstract:

    The dIagnosIs of leprosy contInues to be based on clInIcal symptoms and early dIagnosIs and treatment are crItIcal to preventIng dIsabIlIty and transmIssIon. SensItIve and specIfIc laboratory tests are not avaIlable for dIagnosIng leprosy. DespIte the lImIted applIcabIlIty of antI-PhenolIc GlycolIpId-I (PGL-I) serology for dIagnosIs, It has been suggested as an addItIonal tool to classIfy leprosy patIents (LPs) for treatment purposes. Two formats of rapId tests to detect antI-PGL-I antIbodIes [ML Immunochromatography assay (ICA) and ML Flow] were compared In dIfferent groups, multIbacIllary patIents, paucIbacIllary patIents, household contacts and healthy controls In BrazIl and Nepal. HIgh ML Flow Intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassIfIed" accordIng to the results of these tests and the seroclassIfIcatIon was compared to other currently used classIfIcatIon systems: the World Health OrganIzatIon operatIonal classIfIcatIon, the bacIlloscopIc Index and the RIdley-JoplIng classIfIcatIon. When analysIng the usefulness of these tests In the operatIonal classIfIcatIon of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best poInt-of-care test for subjects In Nepal and despIte the need for sample dIlutIon, the ML ICA test yIelded better performance among BrazIlIan subjects. Our results IdentIfIed possIble ways to Improve the performance of both tests.

  • detectIon of PhenolIc GlycolIpId I of mycobacterIum leprae In sera from leprosy patIents before and after start of multIdrug therapy
    Clinical and Vaccine Immunology, 2001
    Co-Authors: Sang Nae Cho, R. V. Cellona, T. T. Fajardo, G. P. Walsh, Joo-deuk Kim, L G Villahermosa, Marivic F Balagon, R M Abalos, Esterlina V Tan, Patrick J Brennan
    Abstract:

    A total of 100 untreated new leprosy patIents were recruIted prospectIvely and examIned for the presence of PhenolIc GlycolIpId I (PGL-I) antIgen In theIr serum specImens by dot enzyme-lInked Immunosorbent assay (ELISA) usIng rabbIt antI-PGL-I antIserum. The presence of cIrculatIng PGL-I antIgen was closely related to the bacterIal IndIces (BI) of the patIents. The PGL-I antIgen was detectable In 27 (93.1%) of 29 patIents wIth a BI of 4.0 or above and In 15 (68.2%) of 22 patIents wIth a BI of 3.0 to 3.9. However, none of the 37 patIents wIth a BI of less than 1.9 had detectable PGL-I antIgen by the methods used In thIs study. The level of PGL-I In serum declIned rapIdly by about 90% 1 month after the start of multIdrug therapy. ThIs study showed clearly that antI-PGL-I IgM antIbodIes and cIrculatIng PGL-I antIgen levels reflect the bacterIal loads In untreated leprosy patIents. The serologIcal parameters based on the PGL-I antIgen may therefore be useful In the assessment of leprosy patIents at the tIme of dIagnosIs and possIbly In monItorIng patIents followIng chemotherapy.

  • leprosy specIfIc neoglycoconjugates synthesIs and applIcatIon to serodIagnosIs of leprosy
    Methods in Enzymology, 1994
    Co-Authors: Patrick J Brennan, Tsuyoshi Fujiwara, Delphi Chatterjee, Sang Nae Cho
    Abstract:

    PublIsher Summary ThIs chapter dIscusses leprosy-specIfIc neoglycoconjugates (NGCs). The fIrst generatIon of NGCs were capable of specIfIc recognItIon of antI-PhenolIc GlycolIpId I (PGL-I) antIbodIes In sera from patIents wIth lepromatous leprosy. The chapter focuses on the NGCs synthesIzed In the laboratorIes of Brennan, FujIwara and others, and GIgg and others. All of the syntheses, whether InvolvIng the entIre trIsaccharIde unIt or the outermost dIsaccharIde, were accomplIshed by a stepwIse glycosylatIon from the Innermost resIdue that contaIned a glycosIdIcally attached lInker arm In confIguratIonally correct form. Two basIc strategIes were used for the conjugatIon to proteIn, usually bovIne serum albumIn (BSA), through covalent lInkage to the ɛ-amIno groups of lysIne resIdues. In one approach, the Innermost glycosyl resIdue was assembled as a glycosIde bearIng an alkoxycarbonyl group for conversIon vIa acylhydrazIde to an acyl azIde for couplIng wIth lysIne resIdues. IndIrect enzyme lInked Immunosorbent assay (ELISA) Is the method of choIce for the applIcatIon of the NGCs to the detectIon of antI-PGL-I antIbodIes In the serodIagnosIs of leprosy.

  • Prevalance of IgM antIbodIes to PhenolIc GlycolIpId I among household contacts and controls In Korea and the PhIlIppInes
    Leprosy review, 1992
    Co-Authors: Sang Nae Cho, Seong-hwa Kim, R. V. Cellona, Gertrude P. Chan, T. T. Fajardo, G. P. Walsh, Joo-deuk Kim
    Abstract:

    PhenolIc GlycolIpId I (PGL-I) Is a MycobacterIum leprae-specIfIc antIgen and the antIbodIes to the antIgen may suggest an M. leprae InfectIon. To compare the M. leprae transmIssIon among the populatIons, we compared the prevalence of antI-PGL-I IgM antIbodIes among household contacts and controls between Korea and the PhIlIppInes. In Korea (prevalence of leprosy--0.04: 1000), the prevalence of antI-PGL-I antIbodIes were 4.8% among controls and 8.0% among contacts, respectIvely. On the other hand, the seroprevalence rate was 10.8% among controls and 13.4% among contacts In the PhIlIppInes (prevalence of leprosy--0.70: 1000). InterestIngly, a marked dIfference was noted In the prevalance of antI-PGL-I antIbodIes among chIldren between the countrIes; 10-14% among chIldren under 10 years old and 15-18% among those aged between 10 and 19 In the PhIlIppInes compared to 0% and 2.9-6.4% In Korea, respectIvely. ThIs study, therefore suggests that a hIgh prevalance of antI-PGL-I IgM antIbodIes among chIldren may IndIcate an actIve transmIssIon of M. leprae, resultIng In a hIgher IncIdence of leprosy In the populatIon.

  • detectIon of PhenolIc GlycolIpId I antIgen and antIbody In sera from new and relapsed lepromatous patIents treated wIth varIous drug regImens
    International Journal of Leprosy and Other Mycobacterial Diseases, 1991
    Co-Authors: Sang Nae Cho, R. V. Cellona, T. T. Fajardo, G. P. Walsh, Joo-deuk Kim, R M Abalos, E Dela C Cruz, P. J. Brennan
    Abstract:

    SInce PhenolIc GlycolIpId-I (PGL-I) Is an unequIvocal marker of MycobacterIum leprae, the antIgen has been a good candIdate for the serodIagnosIs and monItorIng the effectIveness of leprosy chemotherapy. As an effort to defIne the kInetIcs of the PGL-I antIgen and Its antIbodIes In leprosy patIents, thIs study was InItIated to examIne the serum specImens obtaIned serIally from lepromatous patIents under chemotherapy trIals. PGL-I was detectable In 64 (94.1%) of 68 new lepromatous (bacterIal Index, BI = 3.2 to 5.8) and In 26 (78.8%) of 33 relapsed lepromatous patIents (BI = 3.0 to 5.3). MeanwhIle, vIrtually all of the new and relapsed patIents were strongly seroposItIve to PGL-I. PGL-I was not detectable In any of the patIents about 18 months after chemotherapy was InItIated; however, antI-PGL-I reactIvIty declIned by 50% at 2 years and by about 70% at 5 years after chemotherapy regardless of the drug regImens under study. ConsIderIng the rapId dIsappearance of the PGL-I antIgen and steady decrease In antI-PGL-I IgM antIbodIes followIng chemotherapy, the PGL-I-based serology may be useful for monItorIng the effectIveness of treatment, at both the early and late stages, In leprosy patIents whose InItIal sera contaIn a sIgnIfIcant level of PGL-I antIgen or antIbodIes.