Successful Treatment with Miltefosine of Disseminated Cutaneous Leishmaniasis in a Severely Immunocompromised Patient Infected with HIV-1

Schraner, Christine; Hasse, Barbara; Hasse, Urs; Baumann, Doris; Faeh, Anja; Burg, G; Grimm, Felix; Mathis, Alex; Weber, Rainer; Günthard, Huldrych F.

doi:10.1086/430444

Cited by 51 publications

(33 citation statements)

References 23 publications

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“…This decreased ability for SIV-infected animals to induce this subset of T cells also may explain the high incidence of Leishmania infections that are observed in HIV-infected individuals. [44][45][46] A better understanding of this particular subset of functionally defined CD4 ϩ T cells may be important to understand why these cells are present at low frequencies in SIV-infected RMs and HIV-infected individuals. Furthermore, whether loss of these specific multifunctional cells contributes to other, non-Leishmania, opportunistic infections also should be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…41,42 Furthermore, L major is the causative agent of cutaneous leishmaniasis, 43 a common opportunistic infection in HIV-infected individuals. [44][45][46] To dissect naive (neo) versus memory (recall) MML responses, RMs were split into 3 groups of 5 animals each, and animals were vaccinated for both neo and recall responses in the presence or absence of SIV (Table 1). We studied CD4 ϩ T-cell functionality by measurement of effector functions in response to MML stimulation in vitro, and B-cell functionality by MML-specific antibody production.…”

Section: Introductionmentioning

confidence: 99%

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SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Klatt¹,

Vinton²,

Lynch

et al. 2011

Blood

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HIV infection is characterized by immune system dysregulation, including depletion of CD4 ؉ T cells, immune activation, and abnormal B-and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4 ؉ T cells. However, in SIV-infected animals, CD4 ؉ T-cell functionality decreased after both neo (P ‫؍‬ .0025) and recall (P ‫؍‬ . IntroductionHIV infection is characterized by progressive loss of CD4 ϩ T cells, eventually resulting in opportunistic infections and acquired immunodeficiency syndrome (AIDS) and, in untreated individuals, death. During acute HIV infection, CD4 ϩ T cells are massively infected and rapidly depleted from effector sites, particularly in mucosal tissues, and as infection progresses to chronic disease, there is a progressive, slow loss of peripheral CD4 ϩ T cells. [1][2][3][4][5][6][7] Furthermore, HIV specifically infects activated memory CD4 ϩ T cells, and previous studies have demonstrated that the virus preferentially infects CD4 ϩ T cells where the corresponding antigen is often present at high levels, such as HIV-specific and Mycobacterium tuberculosis-specific cells. 4,8 Hence, the immunodeficiency and dysfunctional immune responses that occur after HIV infection are of particular concern with respect to their role in providing immunity against opportunistic infections. The effectiveness of common vaccines in inducing healthy immune responses among chronically HIV-infected individuals against subsequent infection is decreased. 9 Indeed, the majority of currently effective vaccination approaches induce protective immunity against pathogens by induction of long-term antibody responses specific for the vaccinated antigen. 10 These antibodies are produced mainly by 2 subsets of B cells, plasma cells that reside primarily in the bone marrow and long-lived memory B cells. [11][12][13] Moreover, development of an effective B-cell response is reliant on helper CD4 ϩ T-cell responses that promote antigenspecific B-cell differentiation and antibody class switching. 14 Class switching by B cells from their constitutive expression and production of IgM to other antibody classes (ie, IgG and IgA) is essential to develop an effective immune response, because each type of immunoglobulin has specific functions and sites of activity. 10 IgA may be of particular importance during HIV infection, because IgA plays a significant protective role at mucosal surfaces, 10 and given the common mucosal routes of HIV exposure. 15 Thus, the overall loss of IgA that is observed during HIV infection 16,17 may play a role in driving virus replication at mucosal sites as we...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Klatt¹,

Vinton²,

Lynch

et al. 2011

Blood

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“…Because dogs are never cured parasitologically and given the long half-life of the drug, the lack of European policy might contribute to the emergence of parasites resistant to miltefosine. This resistance could be a problem for European human patients, as miltefosine is being used on a compassionate basis in several European AIDS coinfected patients unresponsive to amphotericin B or pentavalent antimonials (28,29). Furthermore, if dogs infected with miltefosine-resistant strains were to migrate to Latin America, where several countries have registered the drug for human use (currently Colombia, Guatemala, Argentina, Venezuela, Paraguay, Ecuador, and Honduras; 30), the impact might be greater.…”

Section: Import-export Balance Of European Leishmaniasismentioning

confidence: 99%

Spread of Vector-borne Diseases and Neglect of Leishmaniasis, Europe

Dujardin

Campino

Cañavate

et al. 2008

Emerg. Infect. Dis.

355

270

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“…In Guatemala, where Leishmania (Viannia) braziliensis and Leishmania (Leishmania) mexicana are prevalent, a cure rate of 53% with miltefosine was observed (Soto et al 2004). miltefosine has also been successfully used for treating HIV-1 patients who presented with diffuse cutaneous leishmaniasis caused by Leishmania major (Schraner et al 2005). …”

mentioning

confidence: 99%

The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

Morais-Teixeira

Damasceno

Galuppo

et al. 2011

Mem. Inst. Oswaldo Cruz

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The in vitro leishmanicidal activity of miltefosine® (Zentaris GmbH) was assessed against four medically relevant Leishmania species of Brazil: Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) chagasi. The activity of miltefosine against these New World species was compared to its activity against the Old World strain, Leishmania (Leishmania) donovani, which is known to be sensitive to the effects of miltefosine. The IC50 and IC90 results suggested the New World species harboured similar in vitro susceptibilities to miltefosine; however, miltefosine was approximately 20 times more active against the Old World L. (L.) donovani than against the New World L. (L.) chagasi species. The selectivity index varied from 17.2-28.9 for the New World Leishmania species and up to 420.0 for L. (L.) donovani. The differences in susceptibility to miltefosine suggest that future clinical trials with this drug should include a laboratory pre-evaluation and a dose-defining step

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Successful Treatment with Miltefosine of Disseminated Cutaneous Leishmaniasis in a Severely Immunocompromised Patient Infected with HIV-1

Cited by 51 publications

References 23 publications

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Spread of Vector-borne Diseases and Neglect of Leishmaniasis, Europe

The in vitro leishmanicidal activity of hexadecylphosphocholine (miltefosine) against four medically relevant Leishmania species of Brazil

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