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The unwelcome trio: HIV plus cutaneous and visceral leishmaniasis!
Dermatologic Therapy
Abstract
Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of ‘pathologic alliances’, in order to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti-leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established.
... https://www.id-press.eu/mjms/index Treatment is difficult in immunocompromised people, because of the role of both constitutive immunodepression and Leishmania-related immunodepression on the response to the infection [28] [31] [32] [33] [34]. ...
... Leishmaniasis is a parasitic disease affecting both animals and humans, acquired with the bite of sand flies or, in Injection Drug Users (IDUs), with contaminated needles, still hypoendemic in Sicily and the Mediterranean basin [34] [36]. ...
... It is a known opportunistic disease in People Living with HIV (PLWH), whose immunodeficiency promotes visceral localisation, even though the coinfection prevalence reduced after the introduction of HAART [33] [36] [37]. Moreover, Leishmania spp can promote viral replication and enhance progression to Acquired Immuno-Deficiency Syndrome (AIDS) [34]. As a result, despite the introduction of HAART, relapses are still common, and mortality is three times higher in HIV-Leishmania coinfection than in HIVnegative people affected by Leishmania infection [30] [31]. ...
Leishmaniasis is a parasitic disease affecting both animals and humans, acquired with the bite of sand flies or, in Injection Drug Users (IDUs), with contaminated needles, still hypoendemic in Sicily and the Mediterranean basin. Even though it is responsible for 20,000 to 40,000 deaths per year, this parasitic infection is still considered a neglected tropical disease. People Living with HIV (PLWH) are considered at high-risk of developing Leishmaniasis and, despite the introduction of Highly Active Anti-Retroviral Therapy (HAART), mortality rate and relapses prevalence are still high in coinfected people.
We present a case of HIV-Leishmania coinfection, posing the attention on the atypical signs and symptoms and the importance of thinking about other causes than the HIV infection progression when the patient presents with a worsening of his immune status during HAART.
... Leishmaniasis represents a complex, globally widespread opportunistic infection ranging from the visceral form, also called kala-azar, to mucocutaneous and cutaneous disease [1]. ...
... Leishmaniasis is a parasitic skin and visceral disease of worldwide prevalence, endemic in several regions, including those bordering the Mediterranean Sea. It is usually transmitted by the bite of infected sand flies of the genera Phlebotomus or Lutsomyia, and affects both humans and animals (mainly dogs, rats and rodents) [1,6]. ...
... Interestingly, physicians have increasingly focused on the occurrence of visceral leishmaniasis during the course of immunosuppression, initially in transplant recipients [10], then in HIV patients [1,11] and, more recently, in those who are treated with novel biotechnological drugs for certain immune-mediated, chronic diseases [12]. ...
The long-term use of novel antipsoriatic systemic biotechnological drugs may increase susceptibility to opportunistic infections. Several cases of visceral leishmaniasis have been reported in immunosuppressed individuals, including those who have been treated with tumour necrosis factor alpha (TNFα) blocking agents. Simultaneous occurrence of cutaneous and visceral involvement has been more rarely recorded in the medical literature. Herein, we describe a case of mucosal leishmaniasis occurring in a farmer living in an endemic region, who was treated with golimumab because of psoriatic arthritis. This highlights the importance of recognizing cutaneous lesions as a first indicator of possible underlying kala-azar disease.
... The epidemiological importance and relevance of viral coinfection in the progression of human leishmaniasis is emphasized in HIV1 coinfections studies [9][10][11]. HIV1-Leishmania coinfection is found in several areas in the world and may alter several pathological aspects of visceral and cutaneous leishmaniasis [10,11]. ...
... The epidemiological importance and relevance of viral coinfection in the progression of human leishmaniasis is emphasized in HIV1 coinfections studies [9][10][11]. HIV1-Leishmania coinfection is found in several areas in the world and may alter several pathological aspects of visceral and cutaneous leishmaniasis [10,11]. Recently, in vitro coinfection study models indicated that other exogenous viruses such as lymphocytic choriomeningitis virus (LCMV) and Toscana virus (TOSV), which are not linked to immunodeficiency, can shape the pathology of Leishmania infection via type I interferon (IFN) signaling [12]. ...
Background:
Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection.
Methodology/principal findings:
We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load.
Conclusions:
Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections.
... Facciolà et al., 2017;Guarneri, Tchernev, Bevelacqua, Lotti, & Nunnari, 2016;Nunnari et al., 2012;Pinzone, Berretta, Cacopardo, & Nunnari, 2015). Moreover, HIV-positive patients are commonly affected by skin disorders, which are often associated with high morbidity and mortality (Amerio et al., 2013;Khambaty & Hsu, 2010).In particular, though its prevalence is not the highest among the skin disorders, psoriasis affects PLWH severely and for a longer time than the general population (Menon et al., 2010).HIV-associated psoriasis can be observed in every stage of the HIV infection, but its onset seems to be related to risk factors such as a low CD4+ T-cell count and a known familiarity for the disease (Fernandes, Pinto, & Cardoso, 2011). ...
... On the other hand, the introduction of the highly active antiretroviral therapy or combined antiretroviral therapy (cART) dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life Facciolà et al., 2017;Guarneri et al., 2016;Nunnari et al., 2012;Pinzone et al., 2015). Therefore, it is necessary to find newer and safer therapies to treat PLWH affected by psoriasis. ...
People living with HIV (PLWH) are affected by a higher incidence skin disorders, which are often associated with high morbidity and mortality. In particular, psoriasis affects PLWH severely and for a longer time than the general population. Human immunodeficiency virus (HIV) infection is characterized by a progressive decrease in CD4⁺ T‐cell count, and it could seem paradoxical that psoriasis exacerbations are more frequent in this subset of patients than the general population, even though it is commonly observed at any stage of infection. For a long time, there have been limited therapeutic choices for PLWH affected by psoriasis. The introduction of the combined antiretroviral therapy dramatically changed the natural course of both HIV and psoriasis in PLWH, leading to an improvement of quality and duration of life. However, the clinical severity of psoriasis in PLWH often requires the use of immunosuppressant drugs. Knowledge about their safety and efficacy are limited to case‐reports, small case‐series and studies, therefore their use has not yet entered the routine. Further studies are needed to determine if immunosuppressive drugs can be safely and effectively used in PLWH affected by psoriasis and other autoimmune disorders.
... Mediterranian basin is an endemic region for several parasitoses [18,19]. Among these, cutaneous leishmaniasis is relatively frequent, mostly due to Leishmania infantum , carried by the female sandflies of Phlebotomus perniciosus [20]. ...
... Several drug therapies are effective in the treatment of cutaneous leishmaniasis [19] and antimonials have been widely used in localized forms [21]. In our experience intralesional meglumine antimoniate (Glucantime) is useful and manageable, through the selective inhibition of enzymes involved in parasite anaerobic metabolism, with rapid clinical response and little discomfort for the patient [22]. ...
Hoigne syndrome (HS) is the term coined to describe an acute, non-allergic, psychiatrically based reaction occurring with a wide list of medications, mainly antibiotics. Since its first description by Hoigne and Schoch in 1959, few cases have been reported in medical literature and, although antimicrobials are commonly used, very rarely in dermatology. The authors describe the first case occurred after intralesional administration of meglumine antimoniate and briefly discuss the pathogenetic hypotheses on this atypical adverse drug reaction.
... In immunocompromised patients, such as HIV positive patients, the incidence of more malignant form or the development of multiple tumors seems to be higher than among immunocompetent people. In PLWH these malignancies are often more aggressive compared with the general population and they need multidisciplinary assistance (17)(18)(19)(20)(21)(22)(23)(24)(25)(26). ...
Skin cancers represent the most common human tumors with a worldwide increasing incidence. They can be divided into melanoma and non-melanoma skin cancers (NMSCs). NMSCs include mainly squamous cell (SCC) and basal cell carcinoma (BCC) with the latest representing the 80% of the diagnosed NMSCs. The pathogenesis of NMSCs is clearly multifactorial. A growing body of literature underlies a crucial correlation between skin cancer, chronic inflammation and immunodeficiency. Intensity and duration of immunodeficiency plays an important role. In immunocompromised patients the incidence of more malignant forms or the development of multiple tumors seems to be higher than among immunocompetent patients. With regards to people living with HIV (PLWH), since the advent of combined antiretroviral therapy (cART), the incidence of non-AIDS-defining cancers (NADCs), such as NMSCs, have been increasing and now these neoplasms represent a leading cause of illness in this particular population. PLWH with NMSCs tend to be younger, to have a higher risk of local recurrence and to have an overall poorer outcome. NMSCs show an indolent clinical course if diagnosed and treated in an early stage. BCC rarely metastasizes, while SCC presents a 4% annual incidence of metastasis. Nevertheless, metastatic forms lead to poor patient outcome. NMSCs are often treated with full thickness treatments (surgical excision, Mohs micro-graphic surgery and radiotherapy) or superficial ablative techniques (such as cryotherapy, electrodesiccation and curettage). Advances in genetic landscape understanding of NMSCs have favored the establishment of novel therapeutic strategies. Concerning the therapeutic evaluation of PLWH, it’s mandatory to evaluate the risk of interactions between cART and other treatments, particularly antiblastic chemotherapy, targeted therapy and immunotherapy. Development of further treatment options for NMSCs in PLWH seems needed. We reviewed the literature after searching for clinical trials, case series, clinical cases and available databases in Embase and Pubmed. We review the incidence of NMSCs among PLWH, focusing our attention on any differences in clinicopathological features of BCC and SCC between PLWH and HIV negative persons, as well as on any differences in efficacy and safety of treatments and response to immunomodulators and finally on any differences in rates of metastatic disease and outcomes.
... Immune thrombocytopenic purpura (ITP), otherwise known as idiopathic thrombocytopenic purpura, is defined as isolated thrombocytopenia (platelet count < 100,000/µL) with normal white blood cells and normal hemoglobin in the setting of a generalized purpuric rash. Primary ITP presents without a secondary cause or underlying disorder, whereas secondary ITP is usually drug-induced or systemic illness-induced (systemic lupus erythematosus, HIV, psoriasis, etc.) [76][77][78][79] . ...
Helicobacter pylori is a Gram-negative bacterium identified for the first time about 30 years ago and commonly considered as the main pathogenic factor of gastritis and peptic ulcer. Since then, it was found to be associated with several gastrointestinal and extra-gastrointestinal diseases. Helicobacter pylori is also associated with many skin disorders including, but not limited to, chronic urticaria, rosacea, lichen planus, atopic dermatitis, psoriasis, pemphigus vulgaris, vitiligo, primary cutaneous MALT-type lymphoma, sublamina densa-type linear IgA bullous dermatosis, primary cutaneous marginal zone B-cell lymphomas and cutaneous T-cell pseudolymphoma. Literature up to September 2020 shows that clear evidence exists only for some of the mentioned associations, while in the majority of cases, data appear contrasting. The aim of this review is to summarize the available studies on the topic and draw possible conclusions. Further clinical and laboratory studies are needed to assess the real plausibility and relevance of these associations, as well as the possible role of Helicobacter pylori with the underlying pathogenic mechanisms.
... In addition, HAART has increased people living with HIV (PLWH) survival turning the infection in a chronic disease, burdened with an enhanced rate of some non-AIDS-related diseases such as cardiovascular, neurological, renal, dermatological, and bone disorders (Atteritano et al., 2018;Ceccarelli et al., 2019;Guarneri, Tchernev, Bevelacqua, Lotti, & Nunnari, 2016;Venanzi Rullo et al., 2019). Moreover, the prolonged survival brought an increase in the incidence of AIDS (ADCs) and non-AIDS (NADCs) determined cancers Facciolà et al., 2018). ...
People affected by immunodeficiency, and especially those infected by HIV, are burdened by a higher risk of developing malignancies. It has been estimated that the incidence of melanoma in HIV infected people is 2.6‐fold higher than in uninfected ones. In this group of patients, melanoma shows a more aggressive phenotype and poorer survival rates compared to HIV‐negative people. Standard guidelines of diagnosis and care do not exist yet. Studies suggest high index of suspicion and a low threshold for biopsy in HIV‐positive patients regardless of their CD4+ count and the use of standard surgical margins for re‐excision procedures. In case of diagnosis of melanoma in HIV‐positive patients, a thorough search for metastatic disease is recommended because of the more aggressive course of this cancer in HIV‐positive patients. Moreover, to rapidly find out any recurrence or metastatic disease after treatment, these patients need a close follow up, every 3 months, for the first two years and at least twice yearly thereafter. Although surgery remains the main therapeutic option, application of immune checkpoint‐based immunotherapy is being studied and seems to be promising. The aim of this review is to present the current knowledge and future options for melanoma diagnosis and treatment in people living with HIV. This article is protected by copyright. All rights reserved.
... Due to its atypical presentation, with consequent late detection, amelanotic melanoma is often diagnosed at a late stage of the disease with a worsened prognosis [4,10]. About our case, the confounding anamnesis represented an additional misleading, as the patient came from a rural area endemic for cutaneous leishmaniasis [11,12] and the clinical picture of the condition was also evocative [13]. ...
... Due to its atypical presentation, with consequent late detection, amelanotic melanoma is often diagnosed at a late stage of the disease with a worsened prognosis [4,10]. About our case, the confounding anamnesis represented an additional misleading, as the patient came from a rural area endemic for cutaneous leishmaniasis [11,12] and the clinical picture of the condition was also evocative [13]. ...
Leishmaniasis represents a complex, globally widespread opportunistic infection ranging from the visceral form, also called kala-azar, to the mucocutaneous and cutaneous disease.It is endemic in the Mediterranian Basin, Leishmania infantum being demonstrated as the main causative agent of autochthonous cases in Sicily, Italy. The long-term use of systemic antipsoriatic agents, including biotechnological drugs, may cause a higher susceptibility to opportunistic infections, so physicians maintain a high level of suspicion with treated patients. However, some skin tumours, because of the rare occurrence and/or the atypical clinical features, may mimic another kind of disease thus leading to a delay in diagnosis and treatment. An exemplary case is reported herein.
... Impaired immunity in HIV infection causes the reactivation of latent Leishmania infection, whereas leishmaniasis can also promote HIV virus replication and increases progression to AIDS. [8] Mucocutaneous involvement is not a common presentation in old world leishmaniasis, especially nasal involvement. Mucocutaneous leishmaniasis is usually caused by new world species of Leishmania, but it can also be caused by Leishmania aethiopica and rarely other Leishmania species such as Leishmania tropica. ...
Leishmaniasis is caused by protozoan parasite of genus leishmania. Visceral leishmaniasis, diffuse cutaneous leishmaniasis, and atypical forms of cutaneous leishmaniasis are common in HIV-infected patients. Our patient presented with an obstructive mass in nasal cavity and was diagnosed as a case of mucocutaneous leishmaniasis. Spontaneous healing of lesions in HIV-infected patients is rare rather they are unresponsive to treatment and have frequent relapses, especially in patients with low CD4 count. However, in our patient, the lesion improved significantly after 2 months of highly active antiretroviral therapy and co-trimoxazole prophylaxis. © 2016 Indian Journal of Sexually Transmitted Diseases and AIDS Published by Wolters Kluwer-Medknow.
... The reason for its 6 underestimation probably also lies in the difficult differential diagnosis, including some other animal/human parasitoses [12,13], somewhere equally endemic with similar seasonal variations, characterized by confounding clinical features [14], and requesting adequate therapeutic and pro-phylactic measures, often in absence of exact diagnosis. ...
Trombiculiasis represents a striking emerging infestation in humans,. In fact, the modified lifestyles, the easy and quick traveling around the globe, together with the altered ecology and habits of the parasite Neotrombicula autumnalis, make this original epizoonosis an extraordinary example of synanthropic dermatosis. We present an additional clinical image of this unusual parasite transmission from animals to human, occurring in a trekker in Calabria, Italy.
... 3 It seems that in LL certain strains replicate inside the macrophage, so assuming their ability to evade intracellular destruction or a concomitant defect in the T-cell activation process. 2,3 Leishmania infantum, the most frequent causative agent of CL in our geographic area, have been rarely linked with LL. 1,4 The patient received N-methylglucamine-antimoniate, 1 mL twice-a-week intralesionally (total of 7 doses), with progressive improvement. ...
Lupoid leishmanniasis (LL) is a rare form of cutaneousleishmaniasis (CL) showing a striking resemblance with someother granulomatous skin diseases of inflammatory or infec-tious origin.
With the introduction of HAART, the life expectancy of the patients infected with HIV almost approached that of the general population. The incidence of certain HIV-Associated cancers as Kaposi Sarcoma (KS) and Non-Hodgkin Lymphoma (NHL) decreased, while an increase in Non-AIDS-Defining cancers (NADCs) has been documented. HIV infection is a risk factor for numerous cancers in PLWH. Breast cancer is the most common cancer worldwide among all women. The association between HIV infection and breast cancer has not been thoroughly investigated: when compared to the general population, people living with HIV/AIDS (PLWHA) have a similar or slightly lower risk of breast cancer. Screening tests are essential weapons to fight cancer burden and more effective therapeutic and preventive strategies are needed, especially among PLWHA. Further and more comprehensive studies are needed to better characterize breast cancer among PLWH.
The skin as the largest body organ is an important marker for an underlying HIV infection. There is a broad spectrum of skin symptoms and diseases that can be seen arising as a result of the underlying infection and progressing severity of the disease, enabling the dermatologist to make early diagnosis. Depending on the immune status of the patient, various cutaneous manifestations occur. While the majority of them improve as the immune status stabilizes, some may present a paradox by either worsening or clinically becoming more apparent. Drugs used to treat HIV, such as the highly active antiretroviral therapy (HAART), can themselves lead to significant side effects that manifest on the skin.
Background:
In Senegal, reported cases of cutaneous leishmaniasis are often due to Leishmania major. Immunosuppression related to HIV infection contributes to the emergence of leishmaniasis in humans and to cutaneous localization of viscerotropic species. We report the first observed case in Senegal of opportunistic cutaneous leishmaniasis due to Leishmania infantum associated with HIV.
Patients and methods:
A 5-year-old boy presented crusted ulcerative lesions of the scalp and left forearm, together with axillary and cervical lymphadenopathy present for two months. Direct parasitological examination of the scalp and arm lesions, coupled with liquid aspiration of lymph nodes and bone marrow, enabled identification of amastigote forms of Leishmania. Polymerase chain reaction performed on skin, lymph node and bone marrow biopsy samples allowed identification of L. infantum. The child was positive for HIV1. Treatment of HIV infection and leishmaniasis resulted in clinical improvement.
Discussion:
Co-infection with cutaneous leishmaniasis due to L. infantum and HIV is a complex combination in terms of the related therapeutic issues. The clinical and laboratory outcomes depend on restoration of immunity and on the efficacy, safety and availability of anti-leishmaniasis drugs.
We describe the case of an Italian patient with HIV infection who developed an atypical rash resembling post-kala-azar dermal leishmaniasis (PKDL) when receiving liposomal Amphotericin B (L-AMB) for secondary prophylaxis of visceral leishmaniasis (VL). At the time of PKDL appearance, the patient was virologically suppressed but had failed to restore an adequate CD4+ T-cell count. Histology of skin lesions revealed the presence of a granulomatous infiltrate, with lymphocytes, plasma cells, and macrophages, most of which contained Leishmania amastigotes. Restriction fragment length polymorphism-polymerase chain reaction was positive for Leishmania infantum. Paradoxically, cutaneous lesions markedly improved when a new relapse of VL occurred. The patient received meglumine antimoniate, with a rapid clinical response and complete disappearance of cutaneous rash. Unfortunately, the patient had several relapses of VL over the following years, though the interval between them has become wider after restarting maintenance therapy with L-AMB 4 mg/kg/day once a month. Even if rare, PKDL due to Leishmania infantum may occur in Western countries and represents a diagnostic and therapeutic challenge for physicians. The therapeutic management of both PKDL and VL in HIV infection is challenging, because relapses are frequent and evidence is often limited to small case series and case reports.
Visceral leishmaniasis is hypoendemic in Medi-terranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%–6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasit-emia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemio-logical, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region.
Background
Treatment of Visceral Leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidenceMethods
All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded.ResultsA confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent; 21 (12.6%) patients with immune deficiencies other than HIV infection; 25 (15,1%) coinfected with HIV. Liposomal Amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens including L-AmB were used. Mean dose was 29.4±7.9 mg/Kg in immunocompetent patients, 32.9±8.6 mg/Kg in patients with non-HIV related immunodeficiencies and 40.8±6.7 mg/Kg in HIV-infected patients (p <0.001). The mean number of infusion days was 7.8±3.1 in immunocompetent patients, 9.6±3.9 in non HIV immunodeficient patients and 12.0±3.4 in HIV infected patients (p<0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients; 90.5% among non-HIV immunodeficiencies and 72.0% among HIV patients. Among predictors of primary response to treatment, HIV infection and age held independent association in the final multivariate models, whereas doses and duration of L-AmB treatment were not significantly associated.Conclusions
Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes neither in the immunocompetent nor in the immunocompromised population.
As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 countries and three territories (see 'Leishmaniasis Country Profiles Text S1, S2, S3, S4, S5, S6, S7, S8, S9, S10, S11, S12, S13, S14, S15, S16, S17, S18, S19, S20, S21, S22, S23, S24, S25, S26, S27, S28, S29, S30, S31, S32, S33, S34, S35, S36, S37, S38, S39, S40, S41, S42, S43, S44, S45, S46, S47, S48, S49, S50, S51, S52, S53, S54, S55, S56, S57, S58, S59, S60, S61, S62, S63, S64, S65, S66, S67, S68, S69, S70, S71, S72, S73, S74, S75, S76, S77, S78, S79, S80, S81, S82, S83, S84, S85, S86, S87, S88, S89, S90, S91, S92, S93, S94, S95, S96, S97, S98, S99, S100, S101'). Additional information was collated during meetings conducted at WHO regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy.
Improved treatment approaches are needed for visceral leishmaniasis. We assessed the efficacy and safety of three potential short-course combination treatments compared with the standard monotherapy in India.
Standard treatment (1 mg/kg amphotericin B infusion on alternate days for 30 days, total dose 15 mg/kg) was compared with three drug combinations (single injection of 5 mg/kg liposomal amphotericin B and 7-day 50 mg oral miltefosine or single 10-day 11 mg/kg intramuscular paromomycin; or 10 days each of miltefosine and paromomycin) in an open-label, parallel-group, non-inferiority, randomised controlled trial in two hospital sites in Bihar, India. Patients aged 5-60 years with parasitologically confirmed visceral leishmaniasis were randomly assigned one of the four treatments by the trial statistician by use of a computer-generated list. Clinical assessments were done at the end of treatment (15 days on combination treatment; 31 days for standard treatment) and after 45 days and 6 months. The primary endpoint was definitive cure (defined as no sign or symptom of visceral leishmaniasis and parasitologically cured to the last follow-up). Analyses were done both by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00696969.
Between June, 2008, and July, 2009, 634 patients were assigned amphotericin B (n=157), liposomal amphotericin B with miltefosine (n=160) or paromomycin (n=158), or miltefosine and paromomycin (n=159). 618 patients were in the per-protocol population. There were two relapses in each group. The numbers with definitive cure at 6 months for the intention-to-treat population were 146 (cure rate 93·0%; CI 87·5-96·3) for amphotericin B, 156 (97·5%; 93·3-99·2) for liposomal amphotericin B and miltefosine, 154 (97·5%; 93·24-99·2) for liposomal amphotericin B and paromomycin, and 157 (98·7%; 95·1-99·8) for miltefosine and paromomycin. All combinations were non-inferior to the standard treatment, in both the intention-to-treat and per-protocol populations. Patients in the combination groups had fewer adverse events than did those assigned standard treatment.
Combination treatments for visceral leishmaniasis are efficacious and safe, and decrease the duration of therapy, thereby encouraging adherence and reducing emergence of drug-resistant parasites.
Drugs for Neglected Diseases initiative and the Indian Council of Medical Research.
To date, most Leishmania and human immunodeficiency virus (HIV) coinfection cases reported to WHO come from Southern Europe. Up to the year 2001, nearly 2,000 cases of coinfection were identified, of which 90% were from Spain, Italy, France, and Portugal. However, these figures are misleading because they do not account for the large proportion of cases in many African and Asian countries that are missed due to a lack of diagnostic facilities and poor reporting systems. Most cases of coinfection in the Americas are reported in Brazil, where the incidence of leishmaniasis has spread in recent years due to overlap with major areas of HIV transmission. In some areas of Africa, the number of coinfection cases has increased dramatically due to social phenomena such as mass migration and wars. In northwest Ethiopia, up to 30% of all visceral leishmaniasis patients are also infected with HIV. In Asia, coinfections are increasingly being reported in India, which also has the highest global burden of leishmaniasis and a high rate of resistance to antimonial drugs. Based on the previous experience of 20 years of coinfection in Europe, this review focuses on the management of Leishmania-HIV-coinfected patients in low-income countries where leishmaniasis is endemic.
We present a case of visceral leishmaniasis confirmed after the histological investigation of an ulcerate lesion of the scalp in an HIV-1-infected patient receiving highly active antiretroviral therapy (HAART). Histological examination of the skin lesion revealed a squamous cell carcinoma superinfected by amastigotes of Leishmania infantum from the bloodstream. Because HIV-1-infected individuals can harbour parasitic infections in normal and neoplastic tissue, it is necessary to examine carefully any skin lesions, particularly those with uncommon aspects or a worsening course, to exclude superinfections by unsuspected pathogens.
Cutaneous lesions attributed to Leishmania are very seldom observed in classic Kala-Azar, but recently some reports have mentioned them in patients with HIV infection. We found cutaneous lesions whose biopsy disclosed the presence of Leishmania organisms in six patients of a group of 32 HIV patients with visceral Leishmaniasis. These lesions did not present a uniform or specific appearance, even though they tended to localize symmetrically on acral zones. They consisted of erythematous papules and hypopigmented macules on the dorsa of the hands, feet, and elbows; small subcutaneous nodules on the thighs; and erythematoviolaceous, scaly plaques on the face. These lesions accompanied in every case the other symptoms and/or signs of visceral leishmaniasis, responded to anti-leishmanial treatment, and were sometimes the first indicator of recurrence. The histopathological study was non-specific, but showed in every case the presence of abundant amastigotes within the dermal histiocytes and free in the dermis or subcutaneous tissue. Data from literature review are similar to ours.
Visceral leishmaniasis is an endemic infection in Mediterranean countries, where it has become a frequent complication of acquired immunodeficiency syndrome (AIDS). The incidence of visceral leishmaniasis is increasing in Spain due to human immunodeficiency virus (HIV)-related cases, but some aspects of its epidemiology, clinical features, and management remain unknown. In addition, no comparative clinical studies about the disease in HIV-infected and non-HIV-infected patients have been reported. During a 24-year period, 120 cases of visceral leishmaniasis were diagnosed at our institution and 80 (66%) were associated with HIV infection. The mean age at diagnosis was higher in HIV-infected that in non-HIV-infected patients (33.2 versus 23.2 yr; p = 0.002), but the male/female ratio was similar in both groups. The main risk factor for HIV infection was intravenous drug abuse (78.7%). The clinical presentation of leishmaniasis was similar in both groups, but HIV-infected patients had a lower frequency of splenomegaly than HIV-negative individuals (80.8% versus 97.4%; p = 0.02). HIV-infected patients had a greater frequency and degree of leukopenia, lymphocytopenia, and thrombocytopenia. Most of them were profoundly immunosuppressed (mean CD4+ lymphocyte count, 90 cells/mm3) at the time of diagnosis of leishmaniasis, and 53.7% had AIDS. The sensitivity of serologic studies for Leishmania was significantly lower in HIV-infected than in non-HIV-infected patients (50% versus 80%; p < 0.001), but the diagnostic yield of bone marrow aspirate (67.1% versus 79.4%) and bone marrow culture (62.9% versus 66.6%) was similar in both groups. After initial treatment, the response rate was significantly lower in HIV-infected than in non-HIV-infected individuals (54.8% versus 89.7%; p = 0.001). The relapse rate was 46.2% and 7.5%, respectively (p < 0.001). Secondary prophylaxis with antimonial compounds or amphotericin B seems to be useful in preventing relapses in HIV-infected patients. The mortality rate was higher (53.7% versus 7.5%; p < 0.001) and the median survival time shorter (25 versus > 160 mo; p < 0.001) in AIDS patients than in HIV-negative individuals. Although leishmaniasis could contribute to death in a significant number of HIV-infected patients, it was the main cause of death in only a few of them. The CD4+ lymphocyte count and the use of highly active antiretroviral therapy and secondary prophylaxis for leishmaniasis were the most significant prognostic factors for survival in AIDS patients. Visceral leishmaniasis behaves as an opportunistic infection in HIV-infected individuals and should be considered as an AIDS-defining disease.
The present report deals with an unusual clinical presentation of cutaneous leishmaniasis occurring in an atopic subject and discusses the possible pathogenetic mechanisms with particular attention to the role of nitric oxide in the immunological control against intracellular parasites. The altered balance between TH1 and TH2, typical of atopy, with consequent production of IL-4, might contribute to the high susceptibility to opportunistic infections and to the unusual clinical presentation. Moreover the laxity of the tissue and the great vascularization may enhance cutaneous expression of the Leishmania infestation, producing new aspects which add to the difficulty of diagnosis.
Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
HIV-1 viral load 56 was 44 copies/mL. WBC were 2.600/lL, RBC were 57 3.900.000/lL, HGB was 10,1 g/dL, MCV was 71,5, 58 PLT were 112,000/lL. She was also positive for 59 HCV antibodies. Blood cultures, peripheral blood 60 smear, urine analysis
- Cd41 Her Current
Her current CD41 T-cells were 63/mL (20%)
55 and CD81 T-cells 225/mL (73%), HIV-1 viral load
56 was 44 copies/mL. WBC were 2.600/lL, RBC were
57 3.900.000/lL, HGB was 10,1 g/dL, MCV was 71,5,
58 PLT were 112,000/lL. She was also positive for
59 HCV antibodies. Blood cultures, peripheral blood
60 smear, urine analysis, stool ova did not show
61 abnormalities.
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Clinical use of 247 polymerase chain reaction performed on peripheral 248 blood and bone marrow samples for the diagnosis and 249 monitoring of visceral leishmaniasis in HIV-infected and 250
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- E Longhi
Antinori S, Calattini S, Longhi E, et al. Clinical use of
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Guarneri et al.