Lower Trypanosomatids in HIV/AIDS Patients
Total Page：16
File Type：pdf, Size：1020Kb
Annals ofTropical Medicine &Parasitology ,Vol. 97,Supplement No. 1,S75–S78 (2003) Lower trypanosomatids inHIV/AIDS patients C.CHICHARROand J. ALVAR WHOCollaborating Centre for Leishmaniasis, Serviciode Parasitolog ´õ a,Centro Nacional deMicrobiolog ´õ a,Instituto deSaludCarlos III, Carretera Majadahonda– Pozuelo Km 2, 28220Majadahonda, Madrid, Spain Received andaccepted 30 May 2003 Although the family Trypanosomatidae includesparasites ofplants, insectsand vertebrates,only two generain the family, Leishmania and Trypanosoma ,areusually found in humans. Since1995, however, other monoxenous trypanosomatids have beenisolated fromseveral HIV-positive individuals, in whom the parasitescause either visceralor cutaneous lesions. Theseodd casesare reviewed here. It appears that immunocompromised patients may be vulnerableto infectionwith trypanosomatids (and otherparasites) that eitherfail tosurviveor never cause detectablemorbidity in the immunocompetent. Thefamily Trypanosomatidaeincludes several entirely dermotropic in immunocompetent generawhich undergo cyclical development in patients arecausing visceral leishmaniasis both vertebrate andinvertebrate hosts. Such (VL) inHIV-positive patients (Campino digeneticparasites include the Leishmania et al.,1994; Jime´nez et al.,1995; Gramiccia and Trypanosoma speciesthat causedisease et al.,1995). Perhapsmore surprisingly, inhumans and other mammals. The Phyto- somezymodemes of Lei.infantum have only monas speciesthat parasitiselactiferous plants, everbeen found in cases of Leishmania/HIV the Endotrypanum speciesthat infecttwo- co-infection,and not in immunocompetent andthree-toed sloths, and the so-called humansor dogs (Alvar et al.,1997). Although ‘lowertrypanosomatids’ — the Blastocrithidia , the monoxenousor lower trypanosomatids Crithidia, Herpetomonas and Leptomonas species have neverbeen con rmed as pathogenicin that arerestricted to invertebratehosts — humans,there are several reports of human alsobelong to the Trypanosomatidae. infectionwith suchparasites. These infections Overthe last decade, Leishmania and T. cruzi arereviewed below, with particularemphasis have beenfound to becausing new types onseveral cases of apparent infectionwith ofpathology inimmunosuppressed patients, lowertrypanosomatids in those with HIV/ particularlythose with HIVco-infection. AIDS. InHIV-infected patients, forexample, the re-activation of T. cruzi infectionshas beenassociated with meningo-encephalitis (Rocha et al.,1994; Pacheco et al., 1998a; HUMANINFECTIONS CAUSED BY Silva et al.,1999), gastro-intestinaldisease MONOXENOUS (Ferreira et al.,1997) andcutaneous lesions TRYPANOSOMATIDS (Amato et al.,1997; Sartori et al., 1999). In Europe,zymodemes of Lei.infantum that are In1980, McGheeand Cosgrove (1980) describeda possible Herpetomonas infection Reprint requeststo: J.Alvar. ina womanfrom Texas. Several years later, E-mail: [email protected]; fax: +3491 5097034. agellateparasites isolated from individuals ©2003The Liverpool Schoolof Tropical Medicine DOI:10.1179/ 000349803225002552 76 CHICHARRO ANDALVAR inKenya werefound to bemore like Herpeto- characterizationwith specic probesbased monas and Crithidia species,in terms of their ongenomic or kinetoplast DNA probes iso-enzymesor kinetoplast DNA (kDNA), indicatedthat the parasite was notof a than Leishmania species(Githure et al., 1986; Leishmania species.The microscopical exam- Mebrahtu et al.,1992). Acaseof atypical inationof Giemsa-stainedsmears of aculture VLobservedin Guinea-Bissau, in a 10-year- of the parasite revealedonly promastigotes, oldgirl who was seropositivefor HIV-2 indicatingthat the parasite was probably (Sabbatani et al., 1991), was puzzling not of a Trypanosoma species,and its iso- becauseVL hadnever been described in the enzymepatterns were not similar to thoseof country(WHO, 1984); Sabbatani et al. Crithidiafasciculata , Herpetomonas muscarum , (1991) thoughtthe diseasewas the resultof Leptomonasctenocephali , Blastocrithidia spp or the girl’s infectionwith atrypanosomatid Sauroleishmania spp.In cross-hybridization normallyparasitising reptiles. experiments,no kDNA sequencehomology Dedet et al.(1995) describedan HIV- was observedbetween the unknown agellate positivepatient fromMartinique who had a and Leishmania orseveral genera of lower diVusecutaneousinfection with atrypanoso- trypanosomatids.No infectionsdeveloped matid.Iso-enzymatic characterization showed either when Phlebotomus perniciosus (or that this syndromewas notcaused by aknown Lutzomyialongipalpis ;unpubl.obs.) were fed Leishmania, Sauroleishmania or Trypanosoma experimentallyon the agellateor when species.Although the parasite lookedlike a laboratory miceor hamsterswere inoculated lowertrypanosomatid, the structureof the with it. It ishoped that the currentsequencing kinetoplast,the lack of acytopharynxand of the parasite’s ribosomalDNA willallow agellarcysts andthe absenceof choano- it to beidenti ed more fully (M. I. Jime´nez, mastigoteand epimastigote forms indicated unpubl.obs.). Jime ´nez et al.(1996) believed that it was not Blastocrithidia or Crithidia. that immunocompromisedpatients may be Dedetand Pratlong (2000) thoughtthat vulnerableto diseasecaused by infection the agellatewas probably a(normally) with trypanosomatidsthat arenot generally monoxenousparasite ofinsects,and possibly consideredto bepathogenic in humans. a species of Leptomonas or Herpetomonas . Althoughthe humaninfection described by Theirpatient with the unknown agellate was treatedwith meglumineantimoniate Dedet et al. (1995) was thoughtto bean 1 abnormalityresulting from HIV-attributable (Glucantime ;Specia,Paris), remains alive, immunosuppression,the sameparasite has andhas shownno relapse of herleishmaniasis- recentlybeen isolated from a localized likesymptoms (M. I. Jime´nez,unpubl. obs.). cutaneouslesion on an immunocompetent Almostall of thosewith Leishmania/HIV patient, againon Martinique (Boisseau- co-infectionhave relapsesafter treatmentfor Garsaud et al.,2000). Theresults of DNA theirleishmaniasis (Laguna, 2003). sequencingof selectedgenetic foci indicate InBrazil, Pacheco et al. (1998b) described that this parasite may representa novelclade aagellate,apparently amonoxenoustry- withinthe genus Leishmania (Noyes et al., panosomatid,in a 35-year-old, HIV-positive 2002). manwho had presented with the symptoms In1991, anintravenous-drug user from of VL. Asthis patient livedin an area Madrid,who was infectedwith HIV,was wherecutaneous leishmaniasis caused by foundto besu Veringfrom symptoms typical Lei.braziliensis was endemic,the clinicians ofVLandto beco-infected with aagellate whoexamined him at rstsuspected that his ( Jime´nez et al.,1996). Althoughthe result diseasewas the resultof the visceralization of anIFAT for leishmaniasis was border- of Lei.braziliensis .Thissuspicion was sup- line,with atitre of 1/80, the resultsof portedby apositiveresult in an immuno- iso-enzymaticanalyses and of biochemical uorescencetest forleishmaniasis and by LOWER TRYPANOSOMATIDS ANDHIV 77 the observationof amastigotesin a smearof whopresent with the symptomsof leish- bone-marrowaspirate. Theresults of the iso- maniasisneed to beaware that trypanoso- enzymaticcharacterization of the agellate, matidsother than Leishmania may be the using12 enzymaticsystems, indicated, how- cause. ever,that the parasite didnot belong to the genera Leishmania, Sauroleishmania , Trypano- soma, Endotrypanum , Phytomonas, Crithidia, REFERENCES Blastocrithidia , Leptomonas or Herpetomonas . Hybridizationanalyses, against a panelof Alvar, J., Can˜avate, C., Gutie´rrez-Solar,B., many diVerenttrypanosomati ds,revealed Jime´nez,M. I., Laguna, F., Lo´pez-Ve´lez,R., that the unknown agellate hadkDNA Molina, R. &Moreno,J. (1997). Leishmania and cross-homologyonly with Leptomonaspulex- human immunodeciency virus coinfection: the rst simulantis,aparasite of adog ea. The 10 years. Clinical Microbiology Reviews , 10, 298–319 Amato, J.C.P., Amato-Neto, V., Amato, V.S., HIV-attributable depressionof the patient’s Duarte, M. I. S., Uip, D.E. &Boulos, M. (1997). immunesystem may have permittedoppor- Leso˜escuta ˆneascomo u´nicasmanifestac ¸o˜es de tunisticparasitism by this trypanosomatid. reativac¸a˜oda infecc¸a˜opelo Trypanosomacruzi em It isperhaps not surprising that (1) indi- receptorade rim por transplante. Revista daSociedade vidualswho have becomeseverely immuno- Brasileirade Medicina Tropical , 30, 61–63. Boisseau-Garsaund, A. M., Cales-Quist, D., Desbois, N., compromisedas the resultof HIVinfection Jouannelle, A., Pratlong, F.&Dedet,J. P. areparticularly prone to symptomatic (2000). Anewcase of cutaneous infection by apre- infectionwith lowertrypanosomatids that sumed monoxenous trypanosomatid in the island of areusually considered non-pathogenic; or Martinique(French West Indies). Transactions ofthe Royal Society ofTropical Medicine andHygiene , 94, (2) the clinicalmanifestations of suchco- 51–52. infectionsresemble those of visceralor Campino, L., Santos-Gomes, G., Pratlong, F., Dedet, cutaneousleishmaniasis. The presence of J.P.&Abranches, P.(1994). HIV- Leishmania symptomaticinfection with lowertrypano- co-infectionin Portugal: isolation of Leishmania somatidsin immunocom petentpatients infantum MON-24. Transactions ofthe Royal Society ofT ropicalMedicine andHygiene , 88, 394. (Boisseau-Garsaud et al.,2000) ismuch Dedet,J. P.&Pratlong, F.(2000). Leishmania, morestartling. Trypanosoma and monoxenous trypanosomatids as It is diYcultto explainhow any human, emergingopportunistic agents. Journal ofEukaryotic whetherimmunode