Possible Risk Factors in Development of Mucosal Lesions in Leishmaniasis

Cuentas, Elmer Alejandro Llanos; Marsden, P.D.; Cuba, César Augusto Cuba; Campos, Marliane Batista

doi:10.1016/s0140-6736(84)90346-5

Cited by 29 publications

(10 citation statements)

References 2 publications

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“…This finding is of utmost importance in ACL caused by L. braziliensis where long-term ulceration is a risk factor associated with development of mucosal disease. 33,34 We showed that use of antimony in patients with early ACL was associated with a high failure rate. This finding could not be explained by the presence of more risk factors for treatment failure in patients with early ACL.…”

Section: Discussionmentioning

confidence: 97%

“…25,26 It is known that large ulcers, multiple cutaneous lesions and failure with antimony therapy are risk factors for development of mucosal disease. 33,34 Early evidence in one case series suggested high rates of treatment failure despite early treatment of ACL, 27 and in a recent study in Peru, failure in therapeutic response was associated with lesions treated with a duration of less than five weeks. 35 Previously, therapeutic failure or delayed healing had been associated with age, increased duration of disease, presence of multiple lesions, large lesions, parasite species, and helminth infections.…”

Section: Discussionmentioning

confidence: 99%

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Association of Treatment of American Cutaneous Leishmaniasis Prior to Ulcer Development with High Rate of Failure in Northeastern Brazil

Unger¹,

Carvalho²,

Glesby³

et al. 2009

Am J Trop Med Hyg

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Cure rates for American cutaneous leishmaniasis (ACL) range between 60% and 90%. Early evidence suggests lower cure rates for early ACL before the development of the ulceration. We evaluated risk factors for treatment failure in patients with early and classic ulcerative ACL. Patients (n = 136) were 13–60 years of age and had lesions with a duration of 15–90-days. Patients were treated with antimony (20 mg/kg/day for 20 days). The primary outcome was lesion cure by 90 days without recurrence. Patients with early ACL (n = 16) had papules, nodules, plaques, or superficial ulcerations with less than 30 days of illness. Patients with classic ulcerative ACL (n = 120) had ulcerated classic lesions, longer duration, larger lesions, and higher levels of interferon-γ and tumor necrosis factor-α (P ≤ 0.01 for all comparisons). Ulcerated lesions were associated with a lower treatment failure rate compared with early ACL (25.8% versus 75.0%; P < 0.001). Early treatment of ACL does not prevent lesion ulceration and is associated with higher rates of treatment failure.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Association of Treatment of American Cutaneous Leishmaniasis Prior to Ulcer Development with High Rate of Failure in Northeastern Brazil

Unger¹,

Carvalho²,

Glesby³

et al. 2009

Am J Trop Med Hyg

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“…The observation that ML does not occur in clusters of ill individuals may relate to the fact that it tends to be a late outcome among individuals with past history of CL, and chronically infected with the parasite [ 5 , 18 ]. For individuals being inoculated with a ML-prone parasite strain, ML might develop only as a complication of CL when certain host or environmental conditions are present [ 19 , 20 ]. Furthermore, variability in manifestations of this chronic infection might result in different times of mucosal lesions onset among patients, what would interfere with the definition of a cluster, implying temporal and spatial aggregation of cases.…”

Section: Discussionmentioning

confidence: 99%

“…The other possibility would be a more frequent and early treatment of all CL cases in this area, where there is naturally more intensive surveillance for and people’s knowledge about ATL. Treatment delay and failure are risk factors for ML development [ 19 , 20 ]. The early treatment and frequent retreatments might not only prevent part of the ML burden, but also delay its onset and therefore cause the geographic distribution of such cases in this region to be more stationary.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of American tegumentary leishmaniasis in a highly endemic region for Leishmania (Viannia) braziliensis infection in northeast Brazil

et al. 2017

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BackgroundAmerican Tegumentary Leishmaniasis (ATL) caused by Leishmania braziliensis is endemic in Corte de Pedra, Northeast Brazil. Most L. braziliensis infections manifest as localized cutaneous leishmaniasis (CL). Disseminated manifestations include mucosal leishmaniasis (ML), present at a low constant level for several decades, and newly emerging disseminated leishmaniasis (DL). Surprisingly, DL has recently surpassed ML in its spatial distribution. This led us to hypothesize that distinct forms of ATL might spread in different patterns through affected regions.Methodology/Principal findingsWe explored the incidence and geographic dispersion of the three clinical types of ATL over a span of nearly two decades in Corte de Pedra. We obtained the geographic coordinates of the homes of patients with ATL during 1992–1996, 1999–2003 and 2008–2011. The progressive dispersion of ML or DL in each time period was compared to that of CL in 2008–2011 with the Cusick and Edward’s geostatistical test. To evaluate whether ATL occurred as clusters, we compared each new case in 2008–2011 with the frequency of and distance from cases in the previous 3 to 12 months. The study revealed that DL, ML and CL actively spread within that region, but in distinct patterns. Whereas CL and DL propagated in clusters, ML occurred as sporadic cases. DL had a wider distribution than ML until 2003, but by 2011 both forms were distributed equally in Corte de Pedra. The incidence of ML fluctuated over time at a rate that was distinct from those of CL and DL.Conclusions/SignificanceThese findings suggest that CL and DL maintain endemic levels through successive outbreaks of cases. The sporadic pattern of ML cases may reflect the long and variable latency before infected patients develop clinically detectable mucosal involvement. Intimate knowledge of the geographic distribution of leishmaniasis and how it propagates within foci of active transmission may guide approaches to disease control.

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“…CL can disseminate if left undiagnosed and untreated for an extended time period or when occurring in malnourished individuals. Disseminated forms of tegumentary leishmaniasis are also more common in individuals who harbor particular polymorphic risk-associated alleles compared to other genotypes ( Llanos-Cuentas et al, 1984 ; Cabrera et al, 1995 ; Alcais et al, 1997 ; Turetz et al, 2002 ; Castellucci et al, 2005 , 2006 ; Machado-Coelho et al, 2005 ; Salhi et al, 2008 ). Our prior reports suggested that genetic polymorphism of the parasite itself is also associated with the diversity of diseases caused by this parasite ( Schriefer et al, 2004 ; Queiroz et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Early Suppression of Macrophage Gene Expression by Leishmania braziliensis

et al. 2018

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Leishmania braziliensis is an intracellular parasite that resides mostly in macrophages. Both the parasite genome and the clinical disease manifestations show considerable polymorphism. Clinical syndromes caused by L. braziliensis include localized cutaneous (CL), mucosal (ML), and disseminated leishmaniasis (DL). Our prior studies showed that genetically distinct L. braziliensis clades associate with different clinical types. Herein, we hypothesized that: (1) L. braziliensis induces changes in macrophage gene expression that facilitates infection; (2) infection of macrophages with strains associated with CL (clade B), ML (clade C), or DL (clade A) will differentially affect host cell gene expression, reflecting their different pathogenic mechanisms; and (3) differences between the strains will be reflected by differences in macrophage gene expression after initial exposure to the parasite. Human monocyte derived macrophages were infected with L. braziliensis isolates from clades A, B, or C. Patterns of gene expression were compared using Affymetrix DNA microarrays. Many transcripts were significantly decreased by infection with all isolates. The most dramatically decreased transcripts encoded proteins involved in signaling pathways, apoptosis, or mitochondrial oxidative phosphorylation. Some transcripts encoding stress response proteins were up-regulated. Differences between L. braziliensis clades were observed in the magnitude of change, rather than the identity of transcripts. Isolates from subjects with metastatic disease (ML and DL) induced a greater magnitude of change than isolates from CL. We conclude that L. braziliensis enhances its intracellular survival by inhibiting macrophage pathways leading to microbicidal activity. Parasite strains destined for dissemination may exert a more profound suppression than less invasive L. braziliensis strains that remain near the cutaneous site of inoculation.

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Possible Risk Factors in Development of Mucosal Lesions in Leishmaniasis

Cited by 29 publications

References 2 publications

Association of Treatment of American Cutaneous Leishmaniasis Prior to Ulcer Development with High Rate of Failure in Northeastern Brazil

Association of Treatment of American Cutaneous Leishmaniasis Prior to Ulcer Development with High Rate of Failure in Northeastern Brazil

Dynamics of American tegumentary leishmaniasis in a highly endemic region for Leishmania (Viannia) braziliensis infection in northeast Brazil

Early Suppression of Macrophage Gene Expression by Leishmania braziliensis

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