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  IN THIS Article
 ::  Abstract
 ::  The epidemiologi...
 ::  Trends in hiv / ...
 ::  Transmission par...
 ::  People at risk
 ::  Microbiological ...
 ::  Pathogenesis
 ::  Clinical present...
 ::  Diagnostic tools
 ::  Treatment
 ::  Prevention and t...
 ::  Secondary prophy...
 ::  Relapses
 ::  References

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SYMPOSIUM
Year : 2003  |  Volume : 49  |  Issue : 1  |  Page : 39-49

Leishmaniasis in HIV infection.


Internal Medicine Department, Hospital de la Santa Creu i Sant Pau. Av. Sant Antoni Maria Claret 167, 08025 Barcelona. Catalonia. Spain. , Spain

Correspondence Address:
R Paredes
Internal Medicine Department, Hospital de la Santa Creu i Sant Pau. Av. Sant Antoni Maria Claret 167, 08025 Barcelona. Catalonia. Spain.
Spain
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.929

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 :: Abstract 

Herein we review the particular aspects of leishmaniasis associated with HIV infection. The data in this review are mainly from papers identified from PubMed searches and from papers in reference lists of reviewed articles and from the authors' personal archives. Epidemiological data of HIV/Leishmania co-infection is discussed, with special focus on the influence of Highly Active Antiretroviral Therapy (HAART) on incidence of leishmaniasis and transmission modalities. Microbiological characteristics, pathogenesis, clinical presentation and specific treatment of the co-infection are also presented.


Keywords: AIDS-Related Opportunistic Infections, diagnosis,drug therapy,epidemiology,parasitology,Animal, Antimony, therapeutic use,Antiprotozoal Agents, therapeutic use,Antiretroviral Therapy, Highly Active, HIV, pathogenicity,HIV Infections, complications,drug therapy,Human, Leishmania, pathogenicity,Leishmaniasis, complications,diagnosis,drug therapy,epidemiology,Risk Factors,


How to cite this article:
Paredes R, Munoz J, Diaz I, Domingo P, Gurgui M, Clotet B. Leishmaniasis in HIV infection. J Postgrad Med 2003;49:39-49

How to cite this URL:
Paredes R, Munoz J, Diaz I, Domingo P, Gurgui M, Clotet B. Leishmaniasis in HIV infection. J Postgrad Med [serial online] 2003 [cited 2017 Jun 28];49:39-49. Available from: http://www.jpgmonline.com/text.asp?2003/49/1/39/929


The outbreak of HIV/AIDS pandemic during the past 20 years has modified the clinical spectrum of infection by Leishmania spp. in co-infected patients at different levels. The purpose of this review is to outline this emerging background as well as to detail the relevant aspects of such co-infections.


  ::   The epidemiological overlap Top


Despite encouraging news coming from economically developed countries,[1],[2] HIV/AIDS pandemic spread is out of control.[3] Visceral leishmaniasis (VL) is the fourth most common opportunistic parasitic disease in HIV-positive individuals in Spain after pneumocystosis, toxoplasmosis, and cryptosporidiosis.[4] VL promotes the development of AIDS defining conditions[5] and clinical progression, as well as diminishes the life expectancy of HIV-infected subjects. On the other hand, HIV infection increases the risk of developing VL by 100-1000 times in endemic areas[5],[6], reduces the likeliness to therapeutic response and enhances the probability of relapse.[5],[6],[8],[9],[10],[11] Both diseases exert cumulative deficiency of the cellular immune response since both agents damage similar immune resources.[10],[12],[13],[14],[15],[16],[17],[18]

According to data from the World Health Organization,[19] the areas where HIV / Leishmania co-infection is distributed are extensive. So far, 33 countries worldwide have reported co-infections. In southern Europe 25% to 70% of adult VL cases are related to HIV and 1.5% to 9% of AIDS cases suffer from newly acquired or reactivated VL. Of the first 1 700 cases of co-infection which have been reported to the WHO up to 1998, 1 440 cases belonged to south-western Europe.[5] Most co-infections in the Americas are reported in Brazil, where the incidence of AIDS has risen from 0.8 cases per 100 000 inhabitants in 1986 to 10.5 cases per 100 000 inhabitants in 1997. In Africa, the number of cases is expected to rise and is further impaired by social adversities like mass migration, displacement, civil unrest, and war. In Asia, co-infections are increasingly being reported from India, Bangladesh and Nepal, countries that are also facing antimonial resistance.[20],[21] The real impact of HIV/Leishmania co-infection is probably being underestimated owing to constraints in surveillance and reporting of cases.


  ::   Trends in hiv / leishmania co-infection in the “haart-for-some” era Top


It is well known that the advent of highly active antiretroviral therapy (HAART) has modified the natural history of HIV infection and its related opportunistic infections and neoplasms.[1],[2] In addition, it has permitted a partial but substantial recovery of many immune functions in HIV-infected patients,[22] allowing withdrawal of secondary prophylaxis.[23],[24],[25],[26] The beneficial effect of HAART has been demonstrated in other parasitic infections such as toxoplasmosis, cryptosporidiosis and microsporidiosis.[12],[27],[28],[29] A recent study[30] demonstrated that the incidence of VL in HIV-infected patients decreased from 11.6 ± 1.2 per 10 000 persons-years before 1996 to 6.3 ± 0.7 per 10000 persons-years after 1996, the year when HAART was initiated in France. Similar data has been reported from Spain[31] and other reports demonstrate that co-infected patients who receive HAART have a significantly longer survival than those who do not.[10] Nevertheless, the benefits of HAART are only available to 5% or less of HIV-infected patients in the World at present.[3] In countries where HAART is not available, the incidence of opportunistic infections like Pneumocystis carinii is increasing.[32] There is no available data regarding HIV/Leishmania co-infection in developing countries, but several authors suggest that it may be increasing as well.[5],[6],[19],[33]


  ::   Transmission particularities Top


Although the geographic distribution of Leishmania infection is restricted to the areas of distribution of the Phebotomus or Lutzomyia sandflies, HIV infection modifies the traditional zoonotic/anthroponotic patterns of Leishmania transmission. The poor therapeutic outcome, the higher rate of relapses, and the poliparasitic nature of VL in HIV-infected persons, as well as the atypical manifestations of the disease that make diagnosis difficult and the impaired access to health-care resources of co-infected patients, make HIV-infected individuals prone to enlarge the number of human reservoirs in areas where transmission of leishmaniasis is already anthroponotic. In addition, these same characteristics help to create a new focus of anthroponotic transmission in areas where the spread of leishmaniasis has traditionally been zoonotic.

Needle sharing by intravenous drug users (IVDUs) has been proposed as providing an alternative, artificial, and anthroponotic cycle for Leishmania transmission.[5] Multiple indirect data support this hypothesis[8].[30],[34],[37],[39] although similar findings have only been described in South-western Europe, and in fact, no single case of direct acquisition of a primary Leishmania infection derived from syringe use has been reported to date.

Very rarely, Leishmania spp. transmission has been described by alternative means that are also shared by HIV-infection, including blood transfusion,[40],[41],[42],[43],[44],[45],[46] congenital transmission,[46],[47],[48],[49],[50] anal intercourse,[51],[52],[53] and laboratory-acquired.[54] Therefore, although no case of HIV/Leishmania co-infection has been described related to these situations, we must be aware of these potential alternative ways of transmission.


  ::   People at risk Top


Worldwide, the majority of cases of leishmaniasis occur in HIV-negative persons. In this setting, leishmaniasis is still considered a childhood disease.[1],[56],[57],[58],[59] The majority of paediatric patients with leishmaniasis in the Mediterranean basin are HIV-negative.[60] The association of Leishmania infection with AIDS has led to a significant shift in the age of people at risk.

In southwestern Europe 75% of HIV-seronegative and 80 to 83% of HIV-positive patients suffering from VL are men.[5],[10],[33] Men may be at higher risk because of occupational exposure and due to a higher likeliness of intravenous drug use. The limited access of women to healthcare due to cultural and social barriers may underestimate the real impact of leishmaniasis in them. Although some experimental murine models suggest that women are less likely to develop the clinical symptoms of VL than exposed men,[56],[61],[62] it is uncertain whether women are constitutionally protected against Leishmania.

In general, overt clinical leishmaniasis occurs in profoundly immunosuppressed HIV-infected patients. It is considered that 33-78% of co-infected patients with a first episode of VL have previously accomplished AIDS criteria.[4],[10],[36],[63],[65],[66] However, VL can be the first HIV-related serious infection in 13 to 47% of patients.[4],[10],[66] Mean CD4 counts are ??200 cells/mm3 in 62-90% and ? 50 cells/mm3 in 42% of co-infected patients.[8],[11] Studies have suggested that the pre-treatment HIV-1 load may be inversely correlated to the response to anti-Leishmania chemotherapy.[67] Also it is clear that those patients who do not receive HAART are more likely to develop overt clinical leishmaniasis, and to present a higher risk for treatment failure and clinical and parasitological relapse.[8],[10],[11]


  ::   Microbiological features Top


In a majority of HIV-positive individuals, VL is commonly caused by L. infantum or L. donovanii[8] Other Leishmania species like L. braziliensis,[68],[69],[70],[71] L. aethiopica,[72] L.tropica,[73],[74] and L. major[75] have been occasionally described related to the geographical locations of such infections. Nevertheless, there are 3 important considerations to be made regarding the microbiology of HIV-Leishmania co-infections:

a. There is a high variability of L. infantum zymodemes affecting co-infected persons. Up to 150 Leishmania isolates and a total of 17 zymodemes had been described in co-infected patients up to 1997.[8] Indeed, several Leishmania zymodemes can be frequently characterised from single infected individuals. It is uncertain whether this zymodeme variability is exclusively found among IVDUs or if, by the contrary, it is also seen in other HIV risk groups.

b. Several new zymodemes have only been found in HIV-positive patients that had not been reported in immunocompetent patients nor in dogs living in the same geographical areas.

c. The anergic state of HIV-positive individuals permits parasite dissemination regardless of the isolate’s zymodemes. Many theoretically “dermotropic” variants of Leishmania infantum as well as L. (Viannia) braziliensis, L. mexicana and L amazonensis have been described to cause visceral disease in HIV-infected patients.[76],[77],[78],[79] In addition, “viscerotropic” Leishmania spp. variants like L. infantum[80] or L. chagasi[81],[82] can be found in cutaneous lesions related or not to leishmaniasis and even in apparently healthy skin.[83]


  ::   Pathogenesis Top


The co-infection by HIV and Leishmania causes reciprocally enhanced immunologic disturbances.[8] Both infections switch the predominant cellular immune response from Th1 or Th0 to Th2 through complex cytokine-mediated mechanisms leading to the predominance of a humoral response that, according to murine BALBc models,[14] confers susceptibility to both infections. Cytokine disturbances inhibit the production of IFN-?. This exerts a defect in the lytic capacity of macrophages,[13] which cannot eliminate intracellular Leishmania amastigotes through the nitric oxide pathway.[84] The effects of viral infection tend to predominate over those of the parasitic infection.[8] HIV-induced immuno-depression predominates over the cellular response caused by the parasite.[8] HIV-related CD4+ T cell depletion implies a lack of T cells able to recognise Leishmania antigens and to stimulate B-lymphocytes. This leads to an oligoclonal B-cell response, which explains the elevated frequency of false negative Leishmania serology results in co-infected patients.[85] HIV-mediated inhibition of proliferative responses to Leishmania spp.[13] favours the dissemination of leishmaniasis, enables atypical locations of Leishmania parasites, and explains the polyparasitic nature of the disease in HIV positive patients and the uselessness of leishmanin tests in co-infectd patients.

Conversely Leishmania infection increases HIV replication, mainly due chronic immune activation,[95],[96] which is one of the main determinants of HIV-1 disease progression.[86] Immune activation facilitates up-regulation of viral co-receptors (CCR5 and CXCR4), decreased ?-chemokine secretion,[16] enhanced viral entry and integration, as well as viral assembly and/or release.[18] It also leads to an increased secretion of TNF-?, IL-2, IL-4, IL-6, IL-10, and affects the cell cycle.[17],[88] It is indeed associated to several degrees of immune dysfunction, hyporesponsiveness and apoptosis, all leading to enhanced progression of immune deficiency and decreased survival.[89],[90],[91],[92],[93],[94] Compared to HIV-infected patients without leishmaniasis, co-infected patients show a cytokine profile with significant elevations in IL-4, IL-10 and IL-2-receptors, and decreased post-stimulation production of IFN-?.[95],[96],[97],[98] It has been shown that Leishmania infantum-derived lypophosphoglycan (LPG) can induce HIV-1 expression in latently infected peripheral blood mononuclear cells,[15] probably mediated by the secretion of TNF-?.[99] The induction of HIV expression has been suggested by the observations of a progressive increase in HIV-1 RNA load in co-infected patients, in parallel to the increase in IL-4, IL-6 and IL-10 levels.[95] Furthermore, successful treatment of cutaneous, mucocutaneous and VL is associated with a decrease in TNF-? levels.[101] In fact, treatment of leishmanias is in the dually infected patients decreases HIV plasma viral load significantly.[67]


  ::   Clinical presentation Top


Although the majority of Leishmania infections in HIV-positive individuals display clinical features of classic kala-azar,[102],[103] cutaneous and mucocutaneous leishmaniasis, as well as VL in many atypical locations have been increasingly reported. HIV-associated leishmaniasis has five major clinical characteristics:

a. Parasitic dissemination, to the skin in diffuse cutaneous leishmaniasis, or throughout the reticuloendothelial system in visceral and visceralizing syndromes. It has been suggested that almost every organ containing phagocytic cells may eventually become infected by L donovani.[104]

b. Atypical locations, as a consequence of this parasitic dissemination and a defect in cell-mediated immunity.

c. A chronic and relapsing course,[102] with each patient typically experiencing two or three relapses despite proper treatment.

d. Poor response to standard therapy.[105]

e. Lack of anti-Leishmania antibodies, which is seen in many endemic areas.[157]

The clinical features of HIV-related VL are comparable to those of classic disease.[63],[65],[102],[103],[107],[108],[109] The incubation period is variable and may be age-related.[8],[110] During any VL episode, other concomitant opportunistic infections are diagnosed in 42 to 68% of HIV-positive patients.[66],[159] Visceral involvement in HIV-related VL seems to be widespread, neither limited to conventionally described infestation areas nor to the reticuloendothelial system. However, most of the considered “atypical” forms of leishmaniasis have been previously described with variable frequency in immunocompetent individuals,[111],[112],[113],[114] so the term “atypical manifestations” has been challenged.[10]

Systemic Symptoms and Signs

Most patients are male, intravenous drug users with advanced HIV infection and have fever, hepatomegaly and/or splenomegaly, hypergammaglobulinemia, and pancytopenia.[4],[110] Characteristically, splenomegaly is less frequent in HIV-infected patients. Cytopenia is significantly more frequent in HIV-positive patients.[10] Hypergammaglobulinaemia has a limited diagnostic value, because not only it is a frequent finding in VL, but also in HIV-infection per se and in other chronic infections. Constitutional symptoms (asthenia, anorexia and loss of weight) are seen in approximately 50-70% of co-infected patients, and lymphadenopathy ranges 15-60%. The disease tends to disseminate to the skin and other organs, and presentation outside the reticuloendothelial system may mislead the clinician.[110] Frequently, VL is diagnosed during the assessment of a fever of uncertain origin.[115],[116],[117] Seven to 17 percent of fevers of uncertain origin in HIV-positive patients withhold VL, whereas up to 45% of HIV-infected patients who are diagnosed of VL present as fever of unknown origin.[10] It is not uncommon to find Leishmania infection along with other opportunistic infections such as mycobacterioses, pneumonia, cytomegalovirus infections, or AIDS-related neoplasms.

Gastrointestinal Symptoms

Gastrointestinal symptoms are among the most frequent complaints in individuals infected with HIV.[118],[119] Leishmania donovani has been identified in the digestive tracts of 50 percent of HIV-negative patients with VL,[113] and it is increasingly being reported in HIV-positive patients. Any portion of the gastrointestinal tract can undergo parasitisation;[113],[120],[121],[122],[123],[124],[125],[126],[127],[128] jejunal involvement has most frequently been found on biopsies.[120] In HIV-negative patients, the major digestive symptoms of VL include diarrhoea, malabsorption, hypoalbuminemia and weight loss. Unfortunately, these symptoms are non-specific in the patient with AIDS, and thus, other causes must be ruled out.[129] In addition, Leishmania parasites may coexist with many other pathogens or neoplasms in a single digestive area.[105] Therefore, endoscopy and routine biopsy are the best diagnostic tools in HIV-positive patients presenting with unexplained gastrointestinal symptoms.[105],[120],[121],[122],[130] Endoscopy examination shows many variable features, such as normal mucosa, diffuse erythematous oesophageal mucosa with extensive ulceration, erosive gastroduodenitis, gastric ulcers, and multiple reddish colonic lesions.[105],[120] Leishmania parasites have been described coexisting inside Kaposi’s Sarcoma lesions, cytomegalovirus ulcers, or beneath Candida or herpes simplex esophagitis.[105],[120] Therefore, even if the mucosa appears to be normal, multiple random biopsy specimens should be obtained.[105]

Cutaneous Symptoms

Cutaneous involvement of VL is a rare finding,[131] but it is characteristic of HIV-related VL. It is seen in 2–12% of patients with HIV/Leishmania co-infection.[132] It is not infrequent that “viscerotropic” Leishmania species may affect the skin,[131],[133],[134] causing a variable spectrum of lesions. Such lesions may occur simultaneously with visceral involvement and can be papular, maculopapular or nodular. Leishmania amastigotes have been also found in apparently normal skin, infestating sweat ducts,[131] or co-existing with other cutaneous lesions like Kaposi’s sarcoma,[135],[137] herpes simplex and herpes zoster.[138] Sometimes, Leishmania is associated with changes attributable to other dermatological processes like dermatofibromas, psoriasis, Reiter’s syndrome, bacillary angiomatosis, cryptococcosis and oral aphtae, although its presence does not imply a causative role.[80] Unusual skin lesions like linear brown macules on the fingers and palms of the hands, a skin biopsy of a fibrous histiocytoma or even an elevated tattoo, all containing Leishmania amastigotes, have been reported.[139] Leishmaniasis also appeared as a dermatomyositis-like eruption,[140] mucocutaneous and mucosal leishmaniasis, [134] generalised cutaneous leishmaniasis, and post-kala-azar dermal leishmaniasis.[140] As well, primary cutaneous lesions can visceralise in severely immunodepressed patients.[76],[77],[78],[79] Specimens from skin lesions should be obtained whenever there is a suspicion of leishmaniasis in HIV-infected patients. Unless otherwise demonstrated, any cutaneous specimen yielding Leishmania amastigotes in an HIV-infected patient should be considered, in the first place, as a disseminated form of VL rather than a primary cutaneous leishmaniasis.

Respiratory Tract Involvement

Leishmania amastigotes have been found in alveoli and pulmonary septa in up to 75% of HIV/Leishmania co-infected patients in anatomo-pathological studies.[112] However, the clinical significance of this finding remains to be discerned, because the frequent lung involvement usually is not accompanied by symptoms or clinical complications and, when they occur, it is difficult to differentiate the role of Leishmania from other more frequent lung infections.

Renal Involvement and Acute Renal Failure

Renal insufficiency is a rare presentation of leishmaniasis in humans. However, a case of acute renal failure has been recently described as the initial presentation of VL in an HIV-1 infected patient.[142] Glomerulopathy is only associated with visceral disease and not with cutaneous or mucocutaneous forms. Mild proteinuria with benign changes in the urinary sediment (microscopic haematuria and leucocituria) has been reported in up to 60% of HIV-negative patients with kala-azar followed prospectively,[143] although the frequency is unknown for the HIV co-infected. The pathological findings include a glomerulonephritis ranging from purely mesangioproliferative to membranoproliferative, sometimes associated with focal and segmental collapse of capillary loops.[144] Tubulointerstitial damage is usually present.

Miscellaneous Sites of Leishmania Infection

Atypical clinical findings in HIV-related VL suggest that immune failure may facilitate parasitemia and hematogenous spread[145] of leishmanias from typical locations to every part of the body. A retrospective French study found amastigotes in atypical locations in 34% of HIV-infected patients with VL, and these atypical locations where the only diagnostic clue in 15% of cases.[146] Pancreatic,[147] pulmonary,[112] pleural,[148] laryngeal,[104] adrenal,[122] pericardic,[149] myocardic,[122] and lingual[150] leishmanial infections have been described. Importantly, atypical locations can be the first clinical manifestation of VL in the immunodepressed patient.

Mucocutaneous Leishmaniasis in HIV-positive Patients

Mucocutaneous leishmaniasis (MCL) appears in 2 to 3% of all cases of HIV-Leishmania co-infection.[151] Practically all of the Leishmania species can be responsible for MCL lesions. Although the nasal septum and the soft palate are usually affected by MCL due to metastasis from a primary lesion, it can also appear as a primary lesion.[152] Nasal biopsy specimens are commonly needed to elucidate a definitive diagnosis of MCL.


  ::   Diagnostic tools Top


Immune-based Diagnosis

HIV/Leishmania-induced deficit in host’s humoral and cellular responses makes both serological and delayed type IV hypersensitivity-based tests of limited use in co-infected patients. Only about 40-50% of HIV/Leishmania co-infected patients have a positive Leishmania serology.[4],[153] This percentage is inversely correlated with the degree of CD4 T-cell depletion. Anti-Leishmania antibodies in AIDS patients are 50 times lower than in those with an intact immune system.[154] Therefore, with the serological methods many false-negative serology results should be expected in HIV-infected individuals. More sensitive techniques like immunoblotting are being applied which may reach a sensitivity of 70% and a specificity of 73%.[155] However, such serological tests have not been well standarised and there is substantial non-specific cross-reactivity.[156],[157] Hence, it is useful for first diagnosis of leishmaniasis as well as for excluding leishmaniasis when antigenuria is negative, but it is not useful for follow-up, to monitor treatment response of to detect relapses.

Antigen Detection

The polyparasitic nature of leishmaniasis in HIV-1 infected patients permits the detection of Leishmania amastigotes and antigens in peripheral blood, which is unusual in immunocompetent individuals. The direct examination of amastigotes in peripheral blood has permitted the diagnosis of up to 50% of co-infected patients[35],[107] and if the buffy coat is cultured in Novy–McNeal–Nicolle medium, sensitivity may increase to near 70%.[145] In addition to blood samples, methods for detecting Leishmania antigens by Western Blot in urine samples are being implemented. Leishmania antigenuria can persist for several months after the first infection. Hence, it is useful for first diagnosis of leishmaniasis as well as for excluding leishmaniasis when leishmanuria is negative, but it is not useful for follow-up, monitoring, or detecting.

Polymerase Chain Reaction

Although initial PCR techniques requiring tissue samples, had a limited sensitivity and were time consuming,[160],[161],[162],[163],[164] new methods detecting the highly variable regions of the kinetoplast DNA mini-circles improved the sensitivity, specificity and the speed of diagnosis.[165],[166] Such techniques have been combined with ELISA[166] and direct agglutination tests (DAT)[168] with very satisfactory results. Of all the different PCR techniques available, nested-PCR assay is probably the best non-invasive way of diagnosing VL, with a sensitivity of 95.45% in peripheral blood and 100% in bone marrow.[169] Nested-PCR has been useful for monitoring the efficacy of treatment. Relapses after treatment, were predicted 5 months earlier than when predicted using classical diagnostic techniques. Other studies have yielded similar results.[170] However, the cost precludes use of PCR-based tests in underdeveloped countries.

Tissular Parasite Isolation and Culture

The gold standard for the diagnosis of leishmaniasis in HIV-infected patients remains the isolation or identification of the parasite. Up to 10 to 30% of cases of VL in HIV-infected patients are diagnosed from tissue isolates obtained from leishmaniasis in atypical locations. An accurate description of the procedures was provided by Evans.[110] The two most common media utilized in culture are the modified Novy-McNeal-Nicolle medium and a foetal calf serum-supplemented Schneider’s Drosophilla medium.[171],[172] BMAs can yield false-negative results due to various reasons such as the very low number of Leishmania cells in bone marrow or because of haemodiluted samples, or pentamidine or amphotericin B (AMB) given for treatment of pneumocystosis or mycosis.[166] Culture of Leishmania cells from BMAs may improve the direct diagnosis of VL in such patients.[147]


  ::   Treatment Top


Despite the prevalence, clinical implications and epidemiological impact of HIV/Leishmania co-infection, surprisingly scarce data is available regarding the treatment of leishmaniasis in HIV-infected people. The optimal therapy, duration and dosages and particularly, the most adequate treatment and prophylaxis of relapses remain to be established. Overall, treatment approaches are comparable[176] to those of HIV-negative patients with 5 important differences:

a) While the duration of antimonial therapy in HIV-negative patients is 21 days, treatment of co-infected patients should be prolonged until 4 weeks.

b) Treatment of VL is characterised by a low rate of clinical and parasitological response, and frequent relapses. Only about 60% of patients respond clinically or parasitologically to therapy regardless of the regimen used [amphotericin B (AMB) or antimonials], whereas 25-60% of patients experience relapses during the first year after treatment completion.[4],[5],[8],[10],[173]

c) HIV-infected patients are more likely to suffer treatment-related adverse events than the HIV-negative population.[174],[175]

d) There is a role for combining antimonials with allopurinol of IFN-?, which act synergistically with the former compounds, at least in refractory cases and/or relapses. However, there is not enough clinical experience for recommending their use systematically.

e) If available, treatment of HIV-infection with HAART approaches should be stressed.

At present, pentavalent antimonials remain the treatment of choice for HIV-associated VL because their therapeutic efficacy and the rate of adverse events are comparable to those of AMB deoxycolate with less cost. Meglumine antimoniate (20 mg/Kg/day) has demonstrated similar efficacy and toxicity rates than AMB deoxycolate (0.7 mg/Kg/day) both given for 28 days.[173] Generic sodium stibogluconate was comparable to the propietary drug and is substantially cheaper.[175] Due to the emergence of parasite resistance in India,[20] AMB is the treatment of choice in this region. Although lipid formulations are fairly less toxic, antimonials are, in general, considered to be more cost-effective than lipid AMB formulations. Whenever used, allopurinol and IFN-? should be combined with antimonials, and special care should be taken when administering IFN-? to HIV-infected patients suspected of having Kaposi’s sarcoma (KS), since IFN-? could promote the progression of KS lesions. Pentamidine should only be used when no other options are available, specially as a maintenance therapy in co-infection, due to the annoying adverse event profile and an expected lower efficacy. Nevertheless, the high cost at present makes these efficient agents of almost no practical value in less developed countries,[5] so alternative approaches must urgently be developed. Oral miltefosine[21],[177] is a promising alternative for the treatment of Indian VL, but has not been tested yet in HIV/Leishmania co-infected patients.


  ::   Prevention and treatment of relapses Top


Despite its elevated frequency, no specific studies are available comparing the different alternatives to prevent or to treat relapses of VL in HIV co-infected patients. This is an important issue because after “successful” treatment, the parasite persists quiescent in several organs, and continuous exposure to inadequate drug dosages may promote the development of resistance.[8] Up to 7% of VL reactivations in the Mediterranean basin may correspond to re-infections.[178]


  ::   Secondary prophylaxis Top


At present, there is no role for primary prophylaxis against Leishmania infection in HIV-infected patients. Regarding secondary prophylaxis, the most accepted approach includes the monthly administration of 20 mg/Kg meglumine antimoniate or sodium stibogluconate, intravenously or intramuscularly. This is the only strategy that has shown in a non-randomised retrospective trial, some degree of evidence of efficacy.[179] Other alternatives include pentamidine every three or four weeks,[115],[180] liposomal AMB every two weeks,[115],[180] or allopurinol and itraconazole.[115],[182] Further research should clarify the indications and dosages of these regimens. In addition, 2 other important questions remain to be solved. The first is whether HAART mediated immune reconstitution may reduce the likeliness to relapse. Divergent results exist coming from small studies.[10],[183] The second is whether Leishmania prophylaxis can be withdrawn when CD4+ counts surpass 200 cells/mm.[3] However, in daily clinical practice, Leishmania secondary prophylaxis is being withdrawn with CD4 of counts ³ 200 cells/mm3 and, in our clinical experience, no new relapses are being encountered.


  ::   Relapses Top


Relapses have been treated with either antimonials or AMB at standard doses with similar efficacy rates in the clinical setting (personal communication), sometimes during more prolonged periods than usual. Since no specific comparative studies exist, the election of a regimen should be guided by the toxicity profile and patient’s comorbidity.

 
 :: References Top

1.Palella FJ, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection. N Engl J Med 1998;338:853-60.   Back to cited text no. 1    
2.Mocroft A, Vella S, Benfield T L, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. Lancet 1998;352:1725-30.  Back to cited text no. 2    
3.UNAIDS: AIDS Epidemic Update 2002. www.unaids.org.  Back to cited text no. 3    
4.Montalban C, Calleja JL, Erice A, Laguna F, Clotet B, Podzamczer D, et al. Visceral leishmaniasis in patients infected with human immunodeficiency virus. Co-operative Group for the Study of Leishmaniasis in AIDS. J Infect 1990;21:261-70.  Back to cited text no. 4    
5.Guerin PJ, Olliaro P, Sundar S, Boelaert M, Croft SL, Desjeux P, et al. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect Dis 2002;2:494-501.  Back to cited text no. 5    
6.Desjeux P, et al. Leishmania/HIV co-infection in south-western Europe, 1990-1998, retrospective analysis of 965 cases, World Health Organization 2000, WHO/Leish/2000.42.  Back to cited text no. 6    
7.Desjeux P, UNAIDS. Leishmania and HIV in Gridlock. WHO/CTD/LEISH/98.9 Add.I, UNAIDS/98.23.1998. Geneva: WHO, 1998.  Back to cited text no. 7    
8.Alvar J, Canavate C, Gutierrez-Solar B, Jiménez M, Laguna F, López-Vélez R, et al. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin Microbiol Rev 1997;10:298-319.   Back to cited text no. 8    
9.Alvar J. Leishmaniasis and AIDS co-infection the Spanish example. Parasitol Today 1994;10:160-3.  Back to cited text no. 9    
10.Pintado V, Martín-Rabadán P, Rivera ML, Moreno S, Bouza E. Visceral Leishmaniasis in Human Immunodeficiency Virus (HIV)-Infected and Non-HIV-Infected Patients. A Comparative Study. Medicine 2001;80:54-73.  Back to cited text no. 10    
11.Pintado V, López-Vélez R. Leishmaniasis visceral asociada al virus de la inmunodeficiencia humana. Enferm Infecc Microbiol Clin 2001;19:353-7.  Back to cited text no. 11    
12.Kubar J, Marty P, Lelievre A, Quaranta JF, Staccini P, Caroli BC, et al. Visceral leishmaniosis in HIV-positive patients: Primary infection, reactivation and latent infection. Impact of the CD4 T-lymphocyte counts. AIDS 1998;12:2147-53.   Back to cited text no. 12    
13.Wolday D, Akuffo H, Britton S, Hathaway A, Sander B. HIV-1 inhibits Leishmania-induced cell proliferation, but not TNF-alpha and IL-6 production. Scand J Immunol 1994;39:380-6.   Back to cited text no. 13    
14.Reiner, SL, Locksley RM. The regulation of immunity to Leishmania major. Annu Rev Immunol 1995;13:151-77.   Back to cited text no. 14    
15.Bernier, Turco RSJ, Olivier M, Tremblay M. Activation of human immunodeficiency virus type 1 in monocytoid cells by the protozoan parasite Leishmania donovani. J Virol 1995;69:7282-5.   Back to cited text no. 15    
16.Kalinkovich A, Weisman Z, Bentwich Z. Chemokine and chemokine receptors: role in HIV infection. Immunol 1999;68:281-7.  Back to cited text no. 16    
17.Fahey JL. Cytokines, plasma immune asctivation markers, a clinically relevant surrogate markers in human immunodeficiency virus infection. Clin Diag Lab Immunol 1998;597-603.  Back to cited text no. 17    
18.Srebel K, Bour S. Molecular interactions of HIV with human factors. AIDS 1999;13(Suppl A):S13-S24.  Back to cited text no. 18    
19.World Health Organization. Leishmania/HIV co-infection. Epidemiological analysis of 692 retrospective cases. Wkly Epidemiol Rec 1997;72:49-54.  Back to cited text no. 19    
20.Sundar S. Drug resistance in Indian visceral leishmaniasis. Trop Med Int Health 2001;6:849-54.  Back to cited text no. 20    
21.Sundar S, Jha TK, Thakur CP, Engel J, Sindermann H, Fischer C, et al. Oral Miltefosine for Indian Visceral Leishmaniasis. N Engl J Med 2002;347:1739-6.  Back to cited text no. 21    
22.Autran B, Carcelain G, Li TS, et al. Positive Effects of Combined Antiretroviral Therapy on CD4+ T Cell Homeostasis and Function in Advanced HIV Disease. Science 1997;277:112-6.  Back to cited text no. 22    
23.De Quiros J. C. L. B, Miro JM, Pena JM, et al. A Randomized Trial of the Discontinuation of Primary and Secondary Prophylaxis against Pneumocystis carinii Pneumonia after Highly Active Antiretroviral Therapy in Patients with HIV Infection. N Engl J Med 2001;344:159-67.  Back to cited text no. 23    
24.Weverling GJ, Mocroft A, Ledergerber B, et al. Discontinuation of Pneumocystis carinii pneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection. Lancet 1999;353:1293­8.   Back to cited text no. 24    
25.Jouan M, Saves M, Tubiana R, Carcelain G, Cassoux N, Aubron-Olivier C, et al. Discontinuation of maintenance therapy for cytomegalovirus retinitis in HIV-infected patients receiving highly active antiretroviral therapy. AIDS 2001;15:23-31  Back to cited text no. 25    
26.Tural C, Romeu J, Sirera G, Andreu D, Conejero M, Ruiz S, Jou A, Bonjoch A, Ruiz L, Arno A, Clotet B. Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients. J Infect Dis 1998;177:1080-3.  Back to cited text no. 26    
27.Carr A, Marriott D, Field A, Vasak E, Cooper DA. Treatment of HIV-1-associated microsporidiosis and cryptosporidiosis with combination antiretroviral therapy. Lancet 1998;351:256-61.  Back to cited text no. 27    
28.Foudraine NA, Weverling GJ, van Gool T, Roos MT, de Wolf F, Koopmans PP, et al. Improvement of chronic diarrhea in patients with advanced HIV-1 infection during potent antiretroviral therapy. AIDS 1998;12:35-41.  Back to cited text no. 28    
29.Miro JM, Lopez JC, Podzamczer D, Pena JM, Alberdi C, Claramonte X, et al. and the GESIDA 04/98-B Study. Discontinuation of toxoplasmic encephalitis prophylaxis is safe in HIV-1 and T. gondii coinfected patients after immunological recovery with HAART: Preliminary results of the GESIDA 04/98-B study. Abstract 230. San Francisco: Proceedings of the 7th Conference on Retroviruses and Opportunistic Infections, 2000.  Back to cited text no. 29    
30.del Giudice P, Mary-Krause M, Pradier C, Grabar S, Dellamonica P, Marty P et al. Impact of highly active antiretroviral therapy on the incidence of visceral leishmaniasis in a French cohort of patients infected with human immunodeficiency virus. J Infect Dis 2002;186:1366-70.  Back to cited text no. 30    
31.de La Rosa R, Pineda JA, Delgado J, Macias J, Morillas F, Mira JA, et al. Incidence and risk factors for symptomatic visceral leishmaniasis among human immunodeficiency virus type 1-infected patients from Spain in the era of highly active antiretroviral therapy. J Clin Microbiol 2002;40:762-7.  Back to cited text no. 31    
32.Fisk DT, Meshnick S, Kazanjian PH. Pneumocystis carinii pneumonia in patients in the developing world who have acquired immunodeficiency syndrome. Clin Infect Dis 2003;36:70-8.  Back to cited text no. 32    
33.WHO. The world health report 2001. Geneva: WHO, 2001.  Back to cited text no. 33    
34.Gutiérrez J. Prevalence of anti-Leishmania antibodies in parenteral drug addicts: yield value of 2 study techniques. Med Clin 1993;100:168.   Back to cited text no. 34    
35.Medrano FJ, Jimenez-Mejias E, Calderon E, Regordan C, Leal M. An easy and quick method for the diagnosis of visceral leishmaniasis in HIV-1-infected individuals. AIDS 1993;7:1399.   Back to cited text no. 35    
36.Pineda JA, Macias J, Morillas F, Fernandez-Ochoa J, Cara J, de La Rosa R, et al. Evidence of increased risk for Leishmania infantum infection among HIV-seronegative intravenous drug users from southern Spain. Eur J Clin Microbiol Infect Dis 2001;20:354-7.  Back to cited text no. 36    
37.Cruz I, Morales MA, Noguer I, Rodríguez A, Alvar J. Leishmania in discarded syringes from intravenous drug users. Lancet 2002; 359:1124-25.  Back to cited text no. 37    
38.Pineda JA, Martín-Sánchez J, Macías J, Morillas F. Leishmania spp. infection in injecting drug users. Lancet 2002;360:950-1.   Back to cited text no. 38    
39.Molina R, Canavate C, Cercenado E, Laguna F, Lopez-Velez R, Alvar J. Indirect xenodiagnosis of visceral leishmaniasis in 10 HIV-infected patients using colonized Phlebotomus perniciosus. AIDS 1994;8:277-9.  Back to cited text no. 39    
40.Cohen C, Corazza F, Mol PD, et al. Leishmaniasis acquired in Belgium. Lancet 1991;338:128.   Back to cited text no. 40    
41.Kostman R, Barr M, Bengtsson E, et al. Kala-azar transferred by exchange blood transfusion in two Swedish infants. In: Proceedings of the Seventh International Congress of Tropical Medicine and Malaria 1963:384.   Back to cited text no. 41    
42.Mauny I, Blanchot I, Degeihl B, et al. Leishmaniose viscerale chez un nourrisson en Bretagne: discussion sur les modes de transmission hors des zones endemiques. Pediatrie 1993;48:237.   Back to cited text no. 42    
43.Andre R, Brumpt L, Dreyfus B, et al. Cutaneous leishmaniasis, cutaneous-glandular leishmaniasis and transfusional kala-azar. Trop Dis Bull 1958;55:379.   Back to cited text no. 43    
44.Chung H-L, Chow H-K, Lu J-P. The first two cases of transfusion kala-azar. Chinese Med J 1948;66:325.   Back to cited text no. 44    
45.Walker R, ed. Technical Manual. 11th edn. Bethesda, Md: American Association of Blood Banks; 1993. pp.1.   Back to cited text no. 45    
46.Magill AJ. Epidemiology of leishmaniases. Dermatol Clin 1995;13:505-23.   Back to cited text no. 46    
47.Loke Y. Transmission of parasites across the placenta. In: Advances in Parasitology. New York, NY: Academic Press; 1982;21:155.   Back to cited text no. 47    
48.Nuwayri-Salti N, Khansa H. Direct non-insect-vector transmission of Leishmania parasites in mice. Int J Parasitol 1985;15:497.   Back to cited text no. 48    
49.Hiu-Lan Z, Nai-Zheng Z. Studies on leishmaniasis in China: historical background, epidemiology, clinical aspects, legislature and control program. Chinese Med J 1986;99:281.   Back to cited text no. 49    
50.Napier L, Gupta CD. Indian kala-azar in a new born. Indian Med Gazette 1928;62:199.   Back to cited text no. 50    
51.Mebrahtu Y, Hendricks L, Oster C, et al. Leishmania donovani parasites in the nasal secretions, tonsillopharyngeal mucosa, and urine centrifugates of visceral leishmaniasis patients in Kenya. Am J Trop Med Hyg 1989;41:289.   Back to cited text no. 51    
52.Teng C, Forkner C. The presence of infective Leishmania donovani in the urine and prostatic fluid of patients with kala-azar. Chinese Med J 1936;1(suppl):394.   Back to cited text no. 52    
53.Symmers WSC. Leishmaniasis acquired by contagion: a case of marital infection in Britain. Lancet 1960;127.   Back to cited text no. 53    
54.Rosenthal PJ, Chaisson RE, Hadley WK, Leech JH. Rectal leishmaniasis in a patient with acquired immunodeficiency syndrome. Am J Med 1988;84:307-9   Back to cited text no. 54    
55.Herwaldt B, Juranek D. Laboratory-acquired malaria, leishmaniasis, trypanosomiasis, and toxoplasmosis. Am J Trop Med Hyg 1993;48:313.   Back to cited text no. 55    
56.Evans TG, Teixeira MJ, McAuliffe IT, Vasconcelos I, Vasconcelos AW, Sousa Ade A, et al. Epidemiology of visceral leishmaniasis in Northeast Brazil. J Infect Dis 1992;166:1124-32.  Back to cited text no. 56    
57.Belazzoug S. Leishmaniasis in Mediterranean countries. Vet Pathol 1992;44:15.   Back to cited text no. 57    
58.Aggarwal P, Prakash-Wali J. Profile of kala-azar in North India. Asia-Pacific J Public Health 1991;5:90.   Back to cited text no. 58    
59.Heisch R. Studies in leishmaniasis in East Africa, I: the epidemiology of an outbreak of kala-azar in Kenya. Trans R Soc Trop Med Hyg 1954;118:779.  Back to cited text no. 59    
60.Cascio A, Colomba C, Antinori S, Orobello M, Paterson D, Titone L. Pediatric visceral leishmaniasis in Western Sicily, Italy: a retrospective analysis of 111 cases. Eur J Clin Microbiol Infect Dis 2002; 21(4):277-82.  Back to cited text no. 60    
61.Alexander J. Sex differences and cross immunity in DBA/2 mice infected with Leishmania mexicana and L major. Parasitology 1988;96:297.   Back to cited text no. 61    
62.Brabin L, Brabin B. Parasitic infections in women and their consequences. Adv Parasitol 1992;31:1.   Back to cited text no. 62    
63.Lopez-Velez R, Perez-Molina JA, Guerrero A, Baquero F, Villarubia J, Escribano L, et al. Clinico-epidemiological characteristics, prognostic factors and survival analysis of patients coinfected with HIV and Leishmania in an area of Madrid, Spain. Am J Trop Med Hyg 1998;58:436-43.   Back to cited text no. 63    
64.Pineda JA, Gallardo JA, Macias J, Delgado J, Regordan C, Morillas F, et al. Prevalence of and factors associated with visceral leishmaniasis in human immunodeficiency virus type 1-infected patients in southern Spain. J Clin Microbiol 1998;36:2419-22.  Back to cited text no. 64    
65.Ribera E, Cucurull E, Ocana I, Vallespi T, Gasser I, Juste C. [Visceral leishmaniasis in patients with HIV infection.] Enferm Infecc Microbiol Clin 1995;13:73-9.   Back to cited text no. 65    
66.Rosenthal E, Marty P, Poizot-Martin I, Reynes J, Pratlong F, Lafeuillade A, et al. Visceral leishmaniasis and HIV-1 co-infection in southern France. Trans R Soc Trop Med Hyg 1995; 89:159-2.  Back to cited text no. 66    
67.Berhe N, Wolday D, Hailu A, Abraham Y, Ali A, Gebre-Michael T, et al. HIV viral load and response to antileishmanial chemotherapy in co-infected patients. AIDS 1999;13:1921-5.  Back to cited text no. 67    
68.Da-Cruz AM, Machado ES, Menezes JA, Rutowitsch MS, Coutinho SG. Cellular and humoral immune responses of a patient with American cutaneous leishmaniasis and AIDS. Trans R Soc Trop Med Hyg 1992;86:511-2.  Back to cited text no. 68    
69.Echevarria J, Campos P, Chang J, Cuellar L, Gotuzzo E, Paz, et al. Mucocutaneous leishmaniasis and AIDS:case report. Trans R Soc Trop Med Hyg 1993;87:186.  Back to cited text no. 69    
70.Hernández, DE, Oliver M, Martínez C, Planas G. Visceral leishmaniasis with cutaneous and rectal dissemination due to Leishmania braziliensis in AIDS. Int J Dermatol 1995;34:114-5.   Back to cited text no. 70    
71.Machado, ES, Braga MP, Da-Cruz AM, Coutinho SG, Vieira ARM, et al. Disseminated american muco-cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis in a patient with AIDS: a case report. Mem Inst Oswaldo Cruz Rio J 1992;6:1499-503.  Back to cited text no. 71    
72.Berhe N, A Hailu, T Gemetchu. Human immunodeficiency virus and recurrence of cutaneous leishmaniasis long after healed localized cutaneous leishmaniasis due to L aethiopica. Trans R Soc Trop Med Hyg 1995;89:400-1.  Back to cited text no. 72    
73.Centers for Disease Control. Viscerotropic leishmaniasis in persons returning from operation Desert Storm 1990-1991. Morbid Mortal Weekly Rep 1992;41:131-4.  Back to cited text no. 73    
74.Magill, AL,Grogl M, RA, Gasser, Sun W, et al. Visceral infection caused by Leishmania tropica in veterans of operation Desert storm. N Engl J Med 1993;387:1383-7.  Back to cited text no. 74    
75.Gillis, Klaus DS, Schnur LF, Piscopos P, Maayan S, Okon E, et al. Diffusely disseminated cutaneous Leishmania major infection in a child with acquired immunodeficiency syndrome. Pediatr Infect Dis J 199;514:247-9.  Back to cited text no. 75    
76.Silva ES, Pacheco RS, Gontijo CM, Carvalho IR, Brazil IP. Visceral leishmaniasis caused by Leishmania (Viannia) braziliensis in a patient infected with human immunodeficiency virus. Rev Inst Med Trop Sao Paulo 2002;44:145-9.  Back to cited text no. 76    
77.Ramon-Santos C, Hernandez-Montes O, Sanchez-Tejeda G, Monroy-Ostria A. Visceral leishmaniasis caused by Leishmania (L) mexicana in a Mexican patient with human immunodeficiency virus infection. Mem Inst Oswaldo Cruz 2000;95:733-7.  Back to cited text no. 77    
78.Barral A, Pedral-Sampaio D, Grimaldi Junior G, Momen H, McMahon-Pratt D, Ribeiro de Jesus A, et al. Leishmaniasis in Bahia, Brazil:evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am J Trop Med Hyg 1991;44:536-46.  Back to cited text no. 78    
79.Barral A, Badaro R, Barral-Netto M, Grimaldi G Jr, Momem H, Carvalho EM. Isolation of Leishmania mexicana amazonensis from the bone marrow in a case of American visceral leishmaniasis. Am J Trop Med Hyg 1986;35:732-4.   Back to cited text no. 79    
80.Bosch RJ, Rodrigo AB, Sanchez P, de Galvez MV, Herrera E. Presence of Leishmania organisms in specific and non-specific skin lesions in HIV-infected individuals with visceral leishmaniasis. Int J Dermatol 2002;41:670-5.  Back to cited text no. 80    
81.Orsini M, Silva M, Luz ZM, Disch J, Fernandes O, Moreira D, et al. Identification of Leishmania chagasi from skin in Leishmania/HIV co-infection:a case report. Rev Soc Bras Med Trop 2002;35:259-2.  Back to cited text no. 81    
82.Ponce C, Ponce E, Morrison A, Cruz A, Kreutzer R, McMahon-Pratt D, et al. Leishmania donovani chagasi: new clinical variant of cutaneous leishmaniasis in Honduras. Lancet 1991;337:67-70.  Back to cited text no. 82    
83.Gonzalez-Beato MJ, Moyano B, Sanchez C, Gonzalez-Beato MT, Perez-Molina JA, Miralles P, et al. Kaposi’s sarcoma-like lesions and other nodules as cutaneous involvement in AIDS-related visceral leishmaniasis. Br J Dermatol 2000;143:1316-8.  Back to cited text no. 83    
84.Bhattacharyya S, Ghosh S, Dasgupta B, Mazumder D, Roy S, Majumdar S. Chemokine-Induced leishmanicidal Activity in Murine Macrophages via the Generation of Nitric Oxide. J Infect Dis 2002;185:1704-8.  Back to cited text no. 84    
85.Haldar JP, Ghose S, Saha C, Ghose AC. Cell-mediated immune response in Indian kala-azarand post-kala azar dermal leishmaniasis. Infect Inmun 1983;42:702-7.  Back to cited text no. 85    
86.Levy JA. HIV and the Pathogenesis of AIDS 2nd Edn Chapter 9: Effects of HIV on various tissues and organ systems. Edn American Society for Microbiology 1998.  Back to cited text no. 86    
87.Bentwich Z, Maartens G, Torten D, Lal AA, Lal RB. Concurrent infections and HIV pathogenesis. AIDS 2000;14:2071-81.  Back to cited text no. 87    
88.Cohen OJ, Fauci AS. Host factors that affect sexual transmission of HIV. Int J Infect Dis 1998;2:182-5.  Back to cited text no. 88    
89.Grossman Z, Feinberg MB, Paul WE. Multiple modes of cellular activation and virus transmission in HIV infection: a role for chronically and latently infected cells sustaining viral replication. Proc Natl Acad Sci USA 1998;95:6341-9.  Back to cited text no. 89    
90.Bentwich Z, Kalinkoovich A, Weisman Z, Grossman Z. Immune activation in the context of HIV infection. Clin Exp Immunol 1998;111:1-2.  Back to cited text no. 90    
91.Anderson RW, Ascher M, Sheppard HW. Direct HIV cythopaticity cannot account for CD4 decline in AIDS in the presence of homeostasis: a worst-case dynamic analysis. J AIDS 1998;17:245-2.  Back to cited text no. 91    
92.Gougon ML, Montagnier L. Programmed cell eath as a mechanism of CD4 and Cd8 T cell deletion in AIDS. Molecular control and effect of highly active antiretroviral therapy. Ann N Y Acaf Sci 1999;887: 199-212.  Back to cited text no. 92    
93.Lane HC, Gea-Banacloche JC. Lymphocite turnover in the setting of HIV infection. Immunologist 1999;7:124-31.  Back to cited text no. 93    
94.Hazenberg MD, Stuart JW, Otto SA, Borleffs JC, Boucher CA, de Boer RJ, et al. T-cell division in HIV-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART). Blood 2000;95:249-55.  Back to cited text no. 94    
95.Cacopardo, Nigro BL, Preiser W, Fama A, Satariano MI, Braner J, et al. Prolonged Th2 cell activation and increased viral replication in HIV-Leishmania co-infected patients despite treatment. Trans R Soc Trop Med Hyg 1996;90:434-5.  Back to cited text no. 95    
96.Nigro L, Cacopardo B, Preiser W, Braner J, Cinatl J, Palermo F, et al. In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects co-infected with HIV and Leishmania infantum. Am J Trop Med Hyg 1999;60:142-5.  Back to cited text no. 96    
97.Di Piro JT. Cytokine networkswith infection: mycobacterial infections, leishmaniasis, human iummunodeficiency virus and sepsis. Pharmacotherapy 1997;17:205-23.  Back to cited text no. 97    
98.Ribeiro-de-Jesus A, Almeida RP, Lessa H, Bacellar O, Carvalho EM. Cytokine profile and pathology in human leishmaniasis. Braz J Med Biol Res 1998;31:143-48.  Back to cited text no. 98    
99.Folks, TM, Clouse KA, Justement J, Rabson A, Duh E, et al. Tumor necrosis factor alpha induces expression of human inmunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci USA 1989;86:2365-8.   Back to cited text no. 99    
100.Folks, TM, Justement J, Kinter A, Dinarello CA, Fauci AS. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 1987;238:800-2.  Back to cited text no. 100    
101.Blackwell JM. Tumor necrosis factor alpha and mucocutaneous leishmaniasis. Parasitol Today 1999;15:73-5.  Back to cited text no. 101    
102.Montalban C, Martinez-Fernandez R, Calleja JL, Garcia-Diaz JD, Rubio R, Dronda F, et al. Visceral leishmaniasis (kala-azar) as an opportunistic infection in patients infected with the human immunodeficiency virus in Spain. Rev Infect Dis 1989;11:655-60.  Back to cited text no. 102    
103.Sanz MdM, Rubio R, Casillas A, et al. Visceral leishmaniasis in HIV-infected patients. AIDS 1991;5:1272.   Back to cited text no. 103    
104.Gonzalez-Anglada MI, Pena JM, Barbado FJ, Gonzalez JJ, Redondo C, Galera C, et al. Two cases of laryngeal leishmaniasis in patients infected with HIV. Eur J Clin Microbiol Infect Dis 1994;13:509-11.   Back to cited text no. 104    
105.Laguna F, Garcia-Samaniego J, Soriano V, Valencia E, Redondo C, Alonso MJ, et al. Gastrointestinal leishmaniasis in human immunodeficiency virus-infected patients: report of five cases and review. Clin Infect Dis 1994;19:48-53.   Back to cited text no. 105    
106.Badaro R, Carvalho EM, Rocha H, Queiroz AC, Jones TC. Leishmania donovani: an opportunistic microbe associated with progressive disease in three immunocompromised patients. Lancet 1986;1:647-9.   Back to cited text no. 106    
107.Martinez P, de la Vega E, Laguna F, Soriano V, Puente S, Moreno V, et al. Diagnosis of visceral leishmaniasis in HIV-infected individuals using peripheral blood smears. AIDS 1993;7:227-30.   Back to cited text no. 107    
108.Ramos A, Portero JL, Gazapo T, Yebra M, Portero F, Martin T. [Visceral leishmaniasis in immunocompromised patients.] An Med Interna 1998;15:301-4.  Back to cited text no. 108    
109.Reus S, Sanchez R, Portilla J, Boix V, Priego M, Merino E, et al. Visceral leishmaniasis: Comparative study in patients with and without HIV infection. Enferm Infecc Microbiol Clin 1999;17:515-20.   Back to cited text no. 109    
110.Evans TG. Leishmaniasis. Infect Dis Clin North Am 1993;7:527-46.   Back to cited text no. 110    
111.Bryceson AD. Leishmaniasis. In: Cook CG, ed. Manson’s tropical diseases. 1996, 20th edn. London: WB Saunders; pp. 1213.   Back to cited text no. 111    
112.Duarte MIS, da Matta VLR, Corbett CEP, Laurenti MD, Chebabo R, Goto H. Interstitial pneumonitis in human visceral leishmaniasis. Trans R Soc Trop Med Hyg 1989;83:73-6.   Back to cited text no. 112    
113.Muigai R, Gatei D, Shaunak S, et al. Jejunal function and pathology in visceral leishmaniasis. Lancet 1983:27:476-9.   Back to cited text no. 113    
114.Navarro CM, Villanueva MJ, Torre CJ, Ostos AP, Lopez RF, Lopez VP. Isolated laryngeal leishmaniasis in an immunocompetent patient: Successful treatment with surgery. J Laryngol Otol 1994;108:249-51.  Back to cited text no. 114    
115.Alvar J, Gutiérrez-Solar B, Molina R, et al. Prevalence of Leishmania infection among AIDS patients. Lancet 1992;339:264-5.  Back to cited text no. 115    
116.Bissuel F, Leport C, Perronne C, Longuet P, Vilde JL. Fever of unknown origin in HIV-infected patients:a critical analysis of a retrospective series of 57 cases. J Intern Med 1994;236:529-35.   Back to cited text no. 116    
117.Miralles P, Moreno S, Perez-Tascon M, Cosin J, Diaz MD, Bouza E. Fever of uncertain origin in patients infected with the human immunodeficiency virus. Clin Infect Dis 1995;20:872-75.   Back to cited text no. 117    
118.Janoff EN, Smith PD. Perspectives on gastrointestinal infections in AIDS. Gastroenterol Clin North Am 1988;17:451-63.   Back to cited text no. 118    
119.Malebranche R, Arnoux E, Guerin JM, Pierre GD, Laroche AC, Pean-Guichard C, et al. Acquired immunodeficiency syndrome with severe gastrointestinal manifestations in Haiti. Lancet 1983;2:873-8.   Back to cited text no. 119    
120.Villanueva JL, Torre-Cisneros J, Jurado R, et al. Leishmania esophagitis in an AIDS patient: an unusual form of visceral leishmaniasis. Am J Gastroenterol 1994;89:273-5.   Back to cited text no. 120    
121.McBride MO, Fisher M, Skinner CJ, Golden R, Main J. An unusual gastrointestinal presentation of leishmaniasis. Scand J Infect Dis 1995;27:297-8.   Back to cited text no. 121    
122.Mondain-Miton V, Toussaint-Gari M, Hofman P, Marty P, Carles M, De Salvador F, et al. Atypical leishmaniasis in a patient infected with human immunodeficiency virus. Clin Infect Dis 1995;21:663-5.   Back to cited text no. 122    
123.Bryceson ADM. Visceral leishmaniasis (kala-azar, ponos). In: Wyngaarden JB, Smith LH Jr, ed. Textbook of Medicine. 16th edn, Philadelphia: Pa WB Saunders; 1982. pp. 1731-4.   Back to cited text no. 123    
124.Betz P, Elsing C, Purrmann J, et al. Leishmaniasis of the upper gastrointestinal tract in an HIV positive patient. Pathology 1990;11:97-100.   Back to cited text no. 124    
125.Pesce A, Saint-Paul MC, Vinti H, et al. Leishmaniose gastrique chez un malade atteint de syndrome d’immunodéficience acquise. Presse Med 1990;19:178.   Back to cited text no. 125    
126.Banerjee M, Pal A, Ghosh S, Maitra TK. Small intestinal involvement in visceral leishmaniasis. Am J Gastroenterol 1990;85:1433-4.   Back to cited text no. 126    
127.Serrao Neto A, Neves Sousa E, Valente HB, et al. Un cas original de leishmaniose viscerale. Presse Med 1986;27:1286.   Back to cited text no. 127    
128.Sendino A, Barbado J, Mostaza JM, et al. Visceral leishmaniasis with malabsorption syndrome in a patient with acquired immunodeficiency syndrome. Am J Med 1990;87:673-5.   Back to cited text no. 128    
129.Smith PD, Quinn TC, Strober W, Janoff EN, Masur H. NIH conference Gastrointestinal infections in AIDS. Ann Intern Med 1992;116:63-77.   Back to cited text no. 129    
130.Laguna F, Garcia-Samaniego J, Moreno V, Gonzalez-Lahoz JM. Prevalence of gastrointestinal leishmaniasis in Spanish HIV-positive patients with digestive symptoms. Am J Gastroenterol 1994;89:1606.   Back to cited text no. 130    
131.Perrin C, Taillan B, Hofman P, Mondain V, Lefichoux Y, Michiels JF. Atypical cutaneous histological features of visceral leishmaniasis in acquired immunodeficiency syndrome. Am J Dermatopathol 1995;17:145-50.   Back to cited text no. 131    
132.World Health Organization. Report of the consultative meeting on Leishmania/HIV co-infection. WHO/LEISH 1995;95:1-14.   Back to cited text no. 132    
133.Girgla HS, Marsden RA, Singh GM, Ryan TJ. Post kala-azar dermal leishmaniasis. Br J Dermatol 1977;97:307-11.   Back to cited text no. 133    
134.El Safi SH, Peters W, Evans DA, et al. Studies on the leishmaniases in the Sudan, III: clinical and parasitological studies on visceral and mucosal leishmaniasis. Trans Roy Soc Trop Med Hyg 1991;85:465-70.   Back to cited text no. 134    
135.Romeu J, Sirera G, Ferrandiz C, Carreres A, Condom MJ, Clotet B. Visceral leishmaniasis involving lung and a cutaneous Kaposi’s sarcoma lesion. AIDS 1991;5:272.   Back to cited text no. 135    
136.Yebra M, Segovia J, Manzano L, et al. Disseminated to skin kala-azar and the acquired immunodeficiency syndrome. Ann Intern Med 1988;108:490-1.   Back to cited text no. 136    
137.Lahdevirta J, Maury CP, Teppo AM, Repo H. Elevated levels of circulating cachectin/TNF in patients with AIDS. Am J Med 1988;85:289-91.   Back to cited text no. 137    
138.Barrio J, Lecona M, Cosin J, Olalquiaga FJ, Hernanz JM, Soto J. Leishmania infection occurring in herpes zoster lesions in an HIV-positive patient. Br J Dermatol 1996;134:164-6.   Back to cited text no. 138    
139.Colebunders R, Depraetere K, Verstraeten T, Lambert J, Hauben E, Van Marck E, et al. Unusual cutaneous lesions in two patients with visceral leishmaniasis and HIV infection. J Am Acad Dermatol 1999;41:847-50.  Back to cited text no. 139    
140.Dauden E, Penas PF, Rios L, Jimenez M, Fraga J, Alvar J, et al. Leishmaniasis presenting as a dermatomyositis-like eruption in AIDS. J Am Acad Dermatol 1996;35:316-9.   Back to cited text no. 140    
141.Alarcon CR, Garcia C, Garcia E, et al. Leishmaniasis cutanea post kala-azar en un paciente con immunodeficiencia adquirida. Actas Dermo Sif 1987;78:475-7.   Back to cited text no. 141    
142.Clevenbergh P, Okome MN, Benoit S, et al. Acute renal failure as initial presentation of visceral leishmaniasis in an HIV-1 infected patient. Scand J Infect Dis 2002;100:71-4.  Back to cited text no. 142    
143.Dutra MR, Martinelli R, Carvalho EM, et al. Renal involvement in visceral leishmaniasis. Am J Kidney Dis 1985;6:22-7.  Back to cited text no. 143    
144.Van Velthuysen MLF, Florquin S. Glomerulopathy associated with parasitic infections. Clin Microb Rev 2000;13:55-6.  Back to cited text no. 144    
145.Lopez-Velez R, Laguna F, Alvar J, Perez-Molina JA, Molina R, Martinez P, et al. Parasitic culture of buffy coat for diagnosis of visceral leishmaniasis in human immunodeficiency virus-infected patients. J Clin Microbiol 1995;33:937-9.   Back to cited text no. 145    
146.Rosenthal, E, Marty P, le Fichoux Y, Cassuto JP. Clinical manifestations of visceral leishmaniasis associated with HIV infection: a retrospective study of 91 French cases. Ann Trop Med Parasitol 2000; 94:37-42.  Back to cited text no. 146    
147.Berenguer J, Moreno S, Cercenado E, Bernaldo de Quiros JC, Garcia de la Fuente A, et al. Visceral leishmaniasis in patients infected with human immunodeficiency virus (HIV). Ann Intern Med 1989;111:129-32.  Back to cited text no. 147    
148.Greder A, Malet M, Gautier P, et al. Pleurisy revealing leishmaniasis in acquired immunodeficiency syndrome. Presse Med 1989;18:1390-1.   Back to cited text no. 148    
149.Mofredj A, Guerin MJ, Leibinger F, Masmoudi R. Visceral leishmaniasis with pericarditis in an HIV-infected patient. Scand J Infect Dis 2002;34:151-3.  Back to cited text no. 149    
150.Vazquez-Piñeiro T, Fernandez Alvarez JM, Gonzalo Lafuente JC, Cano J, Gimeno M, Berenguer J, et al. Visceral leishmaniasis: a lingual presentation in a patient with HIV infection. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;86:179-82.  Back to cited text no. 150    
151.World Health Organization. AIDS, leishmaniasis dangers of clash highlighted. TDR News 1991;36:1.   Back to cited text no. 151    
152.Miralles ES, Nunez M, Hilara Y, Harto A, Moreno R, Ledo A. Mucocutaneous leishmaniasis and HIV. Dermatology 1994;189:275-7.   Back to cited text no. 152    
153.Gari-Toussaint M, Lelievre A, Marty P, Le Fichoux Y. Contribution of serological tests to the diagnosis of visceral leishmaniasis in patients infected with the human immunodeficiency virus. Trans R Soc Trop Med Hyg 1994;88:301-2.  Back to cited text no. 153    
154.Mary. C, Lamouroux D, Dunan S, Quilici M. Western blot analysis of antibodies to Leishmania infantum antigens: potential of the 14-KD and 16-KD antigens for diagnosis and epidemiologic purposes. Am J Trop Med Hyg 1992;47:764-71.  Back to cited text no. 154    
155.Santos-Gomes G, Gomes-Perreira S, Campino L, Araujo MD, Abranches P. Performance of immunoblotting in diagnosis of visceral Leishmaniasis in human immunodeficiency virus-Leishmania sp.-coinfected patients. J Clin Microbiol 2000;38:175-8.  Back to cited text no. 155    
156.Zijlstra EE, Ali MS, el-Hassan AM, el-Toum IA, Satti M, Ghalib HW, et al. Kala-azar: a comparative study of parasitological methods and the direct agglutination test in diagnosis. Trans R Soc trop Med Hyg 1992;86:505-7.  Back to cited text no. 156    
157.Badaro R, Benson D, Eulalio MC, Freire M, Cunha S, Netto EM, et al. rK39: a cloned antigen of Leishmania chagasi that predicts active visceral leishmaniasis. J Infect Dis 1996;173:758-61.  Back to cited text no. 157    
158.Sundar S, Reed S, Singh V, Kumar P, Murray H. Rapid accurate field diagnosis of Indian visceral leishmaniasis. Lancet 1998;351:563-5.  Back to cited text no. 158    
159.Medrano FJ, Hernandez-Quero J, Jimenez E, Pineda JA, Rivero A, Sanchez-Quijano A, et al. Visceral leishmaniasis in HIV-1-infected individuals: A common opportunistic infection in Spain? AIDS 1992;6: 1499-503.  Back to cited text no. 159    
160.Smyth AJ, Searle S, Ready PD, et al. A kinetoplast DNA probe diagnostic for Leishmania major: sequence homologies between regions of Leishmania minicircles. Mol Biochem Parasitol 1989;37:213-24.   Back to cited text no. 160    
161.Howard MK, Kelly JM, Lane RP, Miles MA. A sensitive repetitive DNA probe that is specific to the Leishmania donovani complex and its use as an epidemiological and diagnostic reagent. Mol Biochem Parasitol 1991;44:63-72.   Back to cited text no. 161    
162.Lopez M, Inga R, Cangalaya M, Echevarria J, Llanos-Cuentas A, Orrego C, et al. Diagnosis of Leishmania using the polymerase chain reaction:a simplified procedure for field work. Am J Trop Med Hyg 1993;49:348-56.   Back to cited text no. 162    
163.de Brujin MH, Labrada LA, Smyth AJ, Santrich C, Barker DC. A comparative study of diagnosis by the polymerase chain reaction and by current clinical methods using biopsies from Colombian patients with suspected leishmaniasis. Trop Med Parasitol 1993;44:201-7.   Back to cited text no. 163    
164.Smyth AJ, Ghosh A, Hassan MQ, Basu D, De Bruijn MH, Adhya S, et al. Rapid and sensitive detection of Leishmania kinetoplast DNA from spleen and blood samples of kala-azar patients. Parasitology 1992;105:183-92.   Back to cited text no. 164    
165.Ravel S, Cuny G, Reynes J, Veas F. A highly sensitive and rapid procedure for direct PCR detection of Leishmania infantum within human peripheral blood mononuclear cells. Acta Trop 1995;59:187-96.  Back to cited text no. 165    
166.Piarroux R, Gambarelli F, Dumon H, Fontes M, Dunan S, Mary C, et al. Comparison of PCR with direct examination of bone marrow aspiration, myeloculture, and serology for diagnosis of visceral leishmaniasis in immunocompromised patients. J Clin Microbiol 1994;32:746-9.  Back to cited text no. 166    
167.Martin-Sanchez J, López-López MC, Acedo-Sanchez C, Castro-Fajardo JJ, Pineda JA, Morillas-Marquez F, et al. Diagnosis of infection with Leishmania infantum using PCR-ELISA. Parasitology 2001;122:607-15.  Back to cited text no. 167    
168.Schalling HD, Schoone GJ, Kroon CC, Hailu A, Chappuis F, Veeken H. Development and application of “simple” diagnostic tools for visceral leishmaniasis. Med Microbiol Immunol 2001;190:69-71.  Back to cited text no. 168    
169.Cruz I, Canavate C, Rubio JM, et al. A nested polumerase chain reaction (Ln-PCR) for diagnosing and monitoring Leishmania infantum infection in patients co-infected with human immunodeficiency virus. Trans R Soc Trop Med Hyg 2002;96(Suppl1):S185-9.  Back to cited text no. 169    
170.Fisa R, Riera C, Ribera E, Gallego M, Portus M. A nested poolymerase Caín reaction for diagnosis and follow-upof human visceral leishmaniasis patients using blood samples. Trans R Soc Trop Med Hyg 2002; 96(Suppl1):S191-4.  Back to cited text no. 170    
171.Hendricks L, Wright N. Diagnosis of cutaneous leishmaniasis by in vitro cultivation of saline aspirates in Schneider’s Drosophila medium. Am J Trop Med Hyg 1979;28:962.   Back to cited text no. 171    
172.Hockmeyer WT, Kager PA, Rees PH, Hendricks LD. The culture of Leishmania donovani in Schneider’s insect medium: its value in the diagnosis and management of patients with visceral leishmaniasis. Trans R Soc Trop Med Hyg 1981;75:861-3.   Back to cited text no. 172    
173.Laguna, F, López-Vélez R, Pulido F, et al. Treatment of visceral leishmaniasis in HIV-infected patients: a randomized trial comparing meglumine antimoniate with amphotericin B. Spanish HIV-Leishmania Study Group. AIDS 1999;13(9):1063-9.  Back to cited text no. 173    
174.Delgado J, Macias J, Pineda JA, Corzo JE, Gonzalez-Moreno MP, de la Rosa R, et al. High frequency of serious side effects of meglumine antimoniate given without an upper limit dose for the treatment of visceral leishmaniasis in human immunodeficiency virus type-1-infected patients. Am J trop Med Hyg 1999;61:766-9.  Back to cited text no. 174    
175.Ritmeijer K, Veeken H, Melaku Y, Leal G, Amsalu R, Seaman J, et al. Ethiopian visceral leishmaniasis:generic and propietary sodium stibogluconate are equivalent: HIV co-infected patients have a poor outcome. Trans R Soc Trop Med Hyg 2001;95:668-72.  Back to cited text no. 175    
176.Paredes R, Laguna F, Clotet B. Leishmaniasis In HIV-infected persons: a review. Journal of the International Association of Physicians in AIDS Care 1997;3:22-39.   Back to cited text no. 176    
177.Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fischer C, et al. Miltefosine, an Oral Agent, for the Treatment of Indian Visceral Leishmaniasis N Engl J Med 1999;341:1795-800  Back to cited text no. 177    
178.Morales MA, Cruz I, Rubio JM, Chicharro C, Canavate C, Laguna F, et al. Relapses vs reinfections in patients coinfected with Leishmania infantum and human immunodeficiency virus type 1. J Infect Dis 2002;185:1533-7.  Back to cited text no. 178    
179.Ribera E, Ocana I, de Otero J, Cortes E, Gasser I, Pahissa A. Prophylaxis of visceral leishmaniasis in human immunodeficiency virus-infected patients. Am J Med 1996;100:496-501.   Back to cited text no. 179    
180.Matheron S, Cabie A, Parquin F, Mayaud C, Roux P, Antoine M, et al. Visceral leishmaniasis and HIV infection: unusual presentation with pleuropulmonar involvement, and effect of secondary prophylaxis. AIDS 1992;6:238-40.   Back to cited text no. 180    
181.McBride M, Linney M, Calydon EJ, Weber J. Visceral. Leishmaniasis following treatment with liposomal amphotericin B. Clin Infect Dis 1994;19:362.   Back to cited text no. 181    
182.Lafeuillade A, Chaffanjon P, Delbeque E, et al. Maintenance itraconazole for visceral leishmaniasis in HIV infection. Am J Med 1992;92:449.  Back to cited text no. 182    



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