Clonal variation within a mucosal isolate derived from a patient with Leishmania (Viannia) braziliensis infection

Cuba-Cuba, César Augusto; Evans, David A.; Rosa, Ana de Cássia; Marsden, Philip D.

doi:10.1590/s0036-46651991000500002

Cited by 9 publications

(8 citation statements)

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“…However, it must be remembered that since cloning one isolate of the first patient discussed here produced a different L. (V.) braziliensis genotype, parasite drug resistance could be variable over time. 8 Since all pentavalent antimonials dissociate or polymerize with time, we shall use a stable, well-defined drug stored at 4ЊC. 9 Another explanation for such repeated relapse is not parasite drug resistance but a failure of the host response.…”

Section: Discussionmentioning

confidence: 99%

Clinical observations of unresponsive mucosal leishmaniasis.

Marsden

Lessa²,

Oliveira³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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Abstract. We report the long-term clinical follow-up of two patients with unresponsive mucosal leishmaniasis due to Leishmania (Viannia) braziliensis from the Três Braços area in Bahia State, Brazil. Both were agricultural male workers with extensive upper respiratory mucosal involvement that was not cured with conventional and experimental therapy.In 1985, we reported two male patients with unresponsive mucosal leishmaniasis who appeared to respond to continuous antimony therapy. 1 At that time, we did not realize how long follow-up was necessary to pronounce clinical cure and both patients subsequently relapsed. In 1986, we reported a recurrence in one of these patients. 2 We now report their long-term follow-up to the end of 1996. Given that a parasitologic cure is difficult to prove and may never occur in some forms of leishmaniasis, 3 response to treatment and relapse were established based on clinical criteria of granuloma activity followed by confirmatory biopsy. All parasite isolations identified by monoclonal antibodies and isoenzyme taxonomy have been Leishmania (Viannia) braziliensis. The last clinical evaluation 1996 showed active mucosal granulomata despite all available treatment. This is the justification for the title of this paper. One of us (PDM) had followed these patients for 18 years. Despite recurrences after treatment, recent granulomata seem less aggressive. Both patients do not have any associated disease or condition such as tuberculosis, schistosomiasis, or blastomycosis, that can explain their peculiar evolution, which we have seen complicating recovery from L. (V.) braziliensis infection in humans. These patients lead normal lives and have growing families. They have spent long periods as hospital inpatients and are not anxious to re-enter the hospital. A brief update of their case histories is given with a tabulated summary of treatment regimens. CASE REPORTSPatient MB (LTB12), a 42-year old man, developed mucosal granulomata at the age of 20. He had no history or sign of a cutaneous lesion. The nose, both palates, and the larynx were affected. Leishmania (Viannia) braziliensis was isolated from a nasal mucosal lesion and characterized by isoenzymes and monoclonal antibodies in 1984 and has been reisolated seven times during the last 20 years. He always responded well to antimony therapy only to relapse. After our last report, he relapsed two years later and subsequent treatment is detailed in Table 1. In our previous report, he appeared to have responded to 85 days of therapy with sodium stibogluconate (Pentostam; Wellcome, London, United Kingdom) (20 mg/kg/day) in the hospital to the tolerance limit. 1 In 1996, he had active granulomata around the nasal septal perfuration confirmed by histology. He also had gran-*Deceased. uloma on the right inferior turbinate and a immunofluorescent antibody titer of 1:80. In our laboratory, a titer Ͼ 1:20 is regarded as significant. Mucosal surfaces affected over time include the nasal septum, inferior turbinates, hard and soft palates, orophary...

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Section: Discussionmentioning

confidence: 99%

Clinical observations of unresponsive mucosal leishmaniasis.

Marsden

Lessa²,

Oliveira³

et al. 1998

The American Journal of Tropical Medicine and Hygiene

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“…the reactivation of persistent infections). However, the exact ratio of relapses: reinfections is difficult to estimate solely on the basis of genetic comparisons of parasite isolates, because there is a finite but unknown probability of re-infection 298 Cutaneous leishmaniasis in the Peruvian Andes 299 with the same parasite variant, and because primary infections may be genetically mixed infections [27].…”

Section: Introductionmentioning

confidence: 99%

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity

et al. 1995

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SUMMARYA prospective longitudinal survey of cutaneous leishmaniasis (Leishmania peruviana) was carried out in Peru on a study population of 4716 persons living in 38 villages (Departments of Lima, Ancash and Piura). Demographic and clinical data were collected from all individuals, and a Montenegro skin test (MST) was carried out on 72 % (3418) of the study population. Each household was revisited at 3-monthly intervals for up to 2 years to detect new leishmaniasis cases; 497 people received a second MST at the end of the study. Analysis of the epidemiological data indicated that (i) 17 % (16/94) of all infections were subclinical, (ii) this percentage increased significantly with age, (iii) clinical infections led to 73-9 % protective immunity (95 % C.I. 53-0-85-5 %) and relatively permanent MST responsiveness (recovery rate = 0-0098/year; 95% C.I. 0000-00020/year), (iv) sub-clinical infections led to protective immunity, which was positively correlated with their MST induration size (increasing by 17-9% per mm; P < 0-0001), and a mean MST recovery rate of 0-414/year (4/421 manmonths), and (v) recurrent leishmaniasis was dominated by reactivations, not by reinfections.

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“…and other kinetoplastids is mainly clonal (8,18,30) and because strains isolated from naturally infected hosts are likely composed of multiclonal parasite associations (7,25), such virulence profiles have to be investigated at the clonal level before any conclusion about the genotypic nature of parasite virulence can be drawn. Thus, this work was undertaken to explore the polymorphism of L. infantum at the intrastrain level and its possible impact on the basis of virulence phenotyping.…”

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confidence: 99%

Virulence ofLeishmania infantumIs Expressed as a Clonal and Dominant Phenotype in Experimental Infections

Garin

Sulahian

Pratlong³

et al. 2001

Infect Immun

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Human Leishmania infantum infection results in a spectrum of clinical expressions ranging from cutaneous to either asymptomatic or fatal visceral disease. In this context, characterization of parasite virulence appears to be relevant as a biological marker of intrinsic parasitic factors that can affect the pathology of leishmaniasis. Since parasite populations in naturally infected hosts are likely to be composed of multiclonal associations, we first explored the biodiversity of parasite virulence at the intrastrain level in vitro and in vivo by using 11 clones isolated from three strains previously known to express different virulence phenotypes in mice. Subsequently, we studied the course of infection in mice inoculated simultaneously or successively with strains or clones showing various virulence phenotypes. Analysis of in vitro growth characteristics showed no differences among clones from the different parental strains. By contrast, in vivo experiments evidenced a marked intrastrain heterogeneity of virulence to mice. One out of five clones obtained from a virulent strain showed a typical virulence phenotype, while the remaining four clones had low-virulence profiles, as did the six clones isolated from two low-virulence strains. In mixed multiclonal infections, the virulence phenotype was expressed as a dominant character over the associated low-virulence clones. After a challenge with either a homologous or a heterologous strain or clone, virulence phenotypes were conserved and expressed as in naive mice independently from the preexisting population. These results strongly suggest that parasite virulence in L. infantum visceral leishmaniasis is clonal and dominant in nature.Parasitic infection with Leishmania spp. results in a broad spectrum of clinical diseases in humans. Leishmania infantum is responsible for most cases of human leishmaniasis in southern Europe and reflects this diversity with proteiform clinical expressions ranging from cutaneous leishmaniasis (CL) to either asymptomatic or fatal visceral leishmaniasis (VL).The varying clinical expression observed in VL depends on complex relationships in which not only the genetic potential (3, 4) and/or immunological status of the host (10,15,20) but also the proper parasite biodiversity (15,16,19,26) appear as determinant factors. Characterization of Leishmania polymorphism at the species and subspecies levels is currently based on isoenzyme and biomolecular analysis. However, identification of biological markers like parasite tropism or virulence remains crucial as a complementary tool to account for the considerable biodiversity of the parasite.In this context, characterization of parasite virulence, i.e., the ability to develop and multiply in vitro and/or in vivo appears particularly relevant for analysis of parasitic factors that can affect the pathology of VL. Using 21 Mediterranean strains of L. infantum isolated from humans, we previously showed that there is a remarkable intraspecific heterogeneity in experimental virulence expression of t...

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Clonal variation within a mucosal isolate derived from a patient with Leishmania (Viannia) braziliensis infection

Cited by 9 publications

References 10 publications

Clinical observations of unresponsive mucosal leishmaniasis.

Clinical observations of unresponsive mucosal leishmaniasis.

Cutaneous leishmaniasis in the Peruvian Andes: an epidemiological study of infection and immunity

Virulence ofLeishmania infantumIs Expressed as a Clonal and Dominant Phenotype in Experimental Infections

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