Showing papers on "Visceral leishmaniasis published in 2002"
TL;DR: Oral miltefosine is an effective and safe treatment for Indian visceral leishmaniasis and may also be helpful in regions where parasites are resistant to current agents.
Abstract: Background There are 500,000 cases per year of visceral leishmaniasis, which occurs primarily in the Indian subcontinent. Almost all untreated patients die, and all the effective agents have been parenteral. Miltefosine is an oral agent that has been shown in small numbers of patients to have a favorable therapeutic index for Indian visceral leishmaniasis. We performed a clinical trial in India comparing miltefosine with the most effective standard treatment, amphotericin B. Methods The study was a randomized, open-label comparison, in which 299 patients 12 years of age or older received orally administered miltefosine (50 or 100 mg [approximately 2.5 mg per kilogram of body weight] daily for 28 days) and 99 patients received intravenously administered amphotericin B (1 mg per kilogram every other day for a total of 15 injections). Results The groups were well matched in terms of age, weight, proportion with previous failure of treatment for leishmaniasis, parasitologic grade of splenic aspirate, and sple...
715 citations
TL;DR: The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leishmania.
Abstract: The group of diseases known as the leishmaniases are caused by obligate intracellular protozoa of the genus Leishmania ([39][1]). Natural transmission of leishmania is carried out by a certain species of sandfly of the genus Phlebotomus (Old World) or Lutzomyia (New World). These are present in
526 citations
TL;DR: New reagents and tools allow the detailed investigation of canine leishmaniasis, permitting the monitoring of the immunological status of dogs in both natural and experimental infections, and are essential to determine the basis of the canine protective immune response and to establish a laboratory model.
437 citations
TL;DR: Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.
Abstract: The elimination of seropositive dogs in Brazil has been used to control zoonotic visceral leishmaniasis but with little success. To elucidate the reasons for this, the infectiousness of 50 sentinel dogs exposed to natural Leishmania chagasi infection was assessed through time by xenodiagnosis with the sandfly vector, Lutzomyia longipalpis. Eighteen (43%) of 42 infected dogs became infectious after a median of 333 days in the field (105 days after seroconversion). Seven highly infectious dogs (17%) accounted for >80% of sandfly infections. There were positive correlations between infectiousness and anti-Leishmania immunoglobulin G, parasite detection by polymerase chain reaction, and clinical disease (logistic regression, r2=0.08-0.18). The sensitivity of enzyme-linked immunosorbent assay to detect currently infectious dogs was high (96%) but lower in the latent period (<63%), and specificity was low (24%). Mathematical modeling suggests that culling programs fail because of high incidence of infection and infectiousness, the insensitivity of the diagnostic test to detect infectious dogs, and time delays between diagnosis and culling.
320 citations
TL;DR: IL-10's deactivating effects regulate outcome in experimental visceral leishmaniasis, and IL-10R blockade represents a potential immuno- and/or immunochemotherapeutic approach in this infection.
Abstract: Interleukin-10 (IL-10) is thought to promote intracellular infection, including human visceral leishmaniasis, by disabling Th1 cell-type responses and/or deactivating parasitized tissue macrophages. To develop a rationale for IL-10 inhibition as treatment in visceral infection, Th1 cytokine-driven responses were characterized in Leishmania donovani-infected BALB/c mice in which IL-10 was absent or overexpressed or its receptor (IL-10R) was blockaded. IL-10 knockout and normal mice treated prophylactically with anti-IL-10R demonstrated accelerated granuloma assembly and rapid parasite killing without untoward tissue inflammation; IL-12 and gamma interferon mRNA expression, inducible nitric oxide synthase reactivity, and responsiveness to antimony chemotherapy were also enhanced in knockout mice. In IL-10 transgenic mice, parasite replication was unrestrained, and except for antimony responsiveness, measured Th1 cell-dependent events were all initially impaired. Despite subsequent granuloma assembly, high-level infection persisted, and antimony-treated transgenic mice also relapsed. In normal mice with established infection, anti-IL-10R treatment was remarkably active, inducing near-cure by itself and synergism with antimony. IL-10's deactivating effects regulate outcome in experimental visceral leishmaniasis, and IL-10R blockade represents a potential immuno- and/or immunochemotherapeutic approach in this infection.
246 citations
TL;DR: Generic stibogluconate enables the cost effective treatment of all forms of leishmaniasis as it remains the most important antileishmanial drug in most parts of the world.
Abstract: Purpose of reviewTreatment of leishmaniasis is far from satisfactory: all antileishmanial drugs are toxic and most have to be used parenterally for prolonged periods, especially for visceral leishmaniasis. In recent years, there has been a steady erosion in the efficacy of pentavalent antimony to cu
151 citations
TL;DR: Data suggest that both VL and CL represent a public health problem in Turkey, but a decline is observed in the number of cases with both infections in recent years.
141 citations
TL;DR: Foxhounds that were > 18 months of age or that had traveled to the southeastern United States were more likely to be diagnosed with visceral leishmaniasis and transmission of Leishmania spp.
Abstract: Although endemic throughout much of the world, autochthonous visceral leishmaniasis has been reported on only 3 previous occasions in North America. After diagnosis of visceral leishmaniasis in 4 foxhounds from a kennel in Dutchess County, New York (index kennel), serum and ethylenediamine-tetraacetic acid (EDTA)-anticoagulated blood were collected from the remaining 108 American or cross-bred foxhounds in the index kennel and from 30 Beagles and Basset Hounds that were periodically housed in the index kennel. Samples were analyzed for antibodies to or DNA of tickborne disease pathogens and Leishmania spp. Most dogs had antibodies to Rickettsia spp., Ehrlichia spp., Babesia spp., or some combination of these pathogens but not to Bartonella vinsonii (berkhoffi). However, DNA of rickettsial, ehrlichial, or babesial agents was detected in only 9 dogs. Visceral leishmaniasis was diagnosed in 46 of 112 (41%) foxhounds from the index kennel but was not diagnosed in any of the Beagles and Basset Hounds. A positive Leishmania status was defined by 1 or more of the following criteria: a Leishmania antibody titer ≥1:64, positive Leishmania polymerase chain reaction (PCR), positive Leishmania culture, or identification of Leishmania amastigotes by cytology or histopathology. The species and zymodeme of Leishmania that infected the foxhounds was determined to be Leishmania infantum MON-1 by isoenzyme electrophoresis. Foxhounds that were >18 months of age or that had traveled to the southeastern United States were more likely to be diagnosed with visceral leishmaniasis. Transmission of Leishmania spp. in kennel outbreaks may involve exposure to an insect vector, direct transmission, or vertical transmission.
139 citations
TL;DR: A polymerase chain reaction-based assay detected kinetoplast DNA of Leishmania chagasi in the blood of eight of 108 asymptomatic persons living with patients with recently diagnosed VL, demonstrating the insensitivity of serology for subclinical infection.
Abstract: In Brazil, programs based on elimination of infected dogs have not curtailed the spread of visceral leishmaniasis (VL), suggesting that other reservoirs of infection exist. Persons with active VL can infect the sand fly vector, but in endemic areas, persons with asymptomatic infections, whose infectivity to sand flies is unknown, are far more numerous. In this study, a polymerase chain reaction-based assay detected kinetoplast DNA of Leishmania chagasi in the blood of eight of 108 asymptomatic persons living with patients with recently diagnosed VL. These eight persons had low or unmeasurable levels of IgG antibodies to Leishmania, demonstrating the insensitivity of serology for subclinical infection. All eight persons had positive leishmanin skin test results, as did 70% of persons living in households of persons with active VL. Even if a small proportion of such asymptomatic persons are infective to sand flies, they represent a formidable reservoir of infection in endemic areas.
132 citations
TL;DR: The results indicate that the rK39-based ELISA is a sensitive and specific diagnostic test for symptomatic VL and can differentiate progressive from self-resolving infection.
Abstract: The sensitivity and specificity of a Leishmania chagasi recombinant K39 (rK39)-based enzyme-linked immunosorbent assay (ELISA) for visceral leishmaniasis (VL) was assessed in Natal, Brazil. Anti-rK39 antibodies were detected in 93.3% of patients with parasitologically confirmed VL (n = 120) and in 33 others with clinically diagnosed disease. Anti-rK39 antibodies decreased significantly following treatment. The presence of antibodies was inversely correlated with development of a positive leishmanin skin test result. Anti-rK39 antibodies were detected in only 2.9% of asymptomatic subjects with a positive skin test result (n = 168). They were not detected in healthy controls (n = 30) or in persons with Chagas' disease (n = 13) or active tuberculosis (n = 31). Antibodies were found in only one of 13 patients with cutaneous leishmaniasis. In contrast, an ELISA using total L. chagasi promastigote antigen was sensitive, but not specific. The results indicate that the rK39-based ELISA is a sensitive and specific diagnostic test for symptomatic VL and can differentiate progressive from self-resolving infection.
121 citations
TL;DR: The aim of this study was to determine the importance of domestic dogs as the reservoir hosts of visceral leishmaniasis in northwest Iran and the impact of dog ownership within villages on child seropositivity.
Abstract: One explanation proposed for the widespread failure to control zoonotic visceral leishmaniasis by culling infected domestic dogs is that wild canids or humans play significant roles in transmission. The aim of this study was to determine the importance of domestic dogs as the reservoir hosts of visceral leishmaniasis in northwest Iran. A random sample of 3,872 children and 199 dogs in 38 villages was surveyed by the direct agglutination test. Dog ownership details among these households were collected by questionnaire. Parasites isolated from 16 patients and 12 dogs were characterized as Leishmania infantum MON-1. Average seroprevalence in dogs (21.6%) was much higher than in children (7%). Child seropositivity increased significantly with village dog density in absolute terms (P < 0.001) and in relation to dog/human ratios (P = 0.028). Dog ownership within villages also was a significant risk factor for child seropositivity (P = 0.003).
TL;DR: The rK39 ELISA is a relatively simple and rapid assay for assessing the infection status of dogs, and is an alternative to IFAT, especially when screening large numbers of samples.
TL;DR: The FML antigen of Leishmania donovani, in combination with either Riedel de Haën (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis and showed significant and specific increases in anti-FML IgG and IgM responses.
TL;DR: The study showed that mass screening of family members and contacts by using anti-rK39 ELISA could be a highly reliable tool for early diagnosis and to plan prophylactic treatment of latently infected asymptomatic carriers to eradicate kala-azar.
Abstract: Clinically visceral leishmaniasis is suspected in only a fraction of infected persons, as the majority of these may not have clinical manifestations and remain asymptomatic. There is scanty information on diagnosing latent infections and predicting disease in asymptomatic persons. We therefore carried out a study on asymptomatic contacts of patients with visceral leishmaniasis and post-kala-azar dermal leishmaniasis by using methods for detection of antibody to recombinant K39 (rK39) antigen. A total of 240 patients with leishmaniasis and 150 asymptomatic contacts were tested for anti-rK39 immunoglobulin G (IgG) and IgA antibodies. Fifty-five asymptomatic persons were found to be seropositive. These individuals were monitored every 3 months for 1 year. On follow-up, 43.9% of the asymptomatic seropositive contacts developed kala-azar within the first 3 months, and a cumulative total of 69% developed kala-azar within 1 year. The rest remained asymptomatic and self-healed the infection. The sensitivity and specificity of rK39 enzyme-linked immunosorbent assay (ELISA) and dipstick tests were 100%, while an in-house-developed latex agglutination test had 80% sensitivity. The antibody profile showed that the IgG anti-rK39 antibodies reached a titer of up to 10−6 within 6 months of infection, started declining thereafter, and completely disappeared in 2 to 3 years in successfully treated cases. Significant titers of IgA antibodies were detectable a little earlier than those of IgG antibodies and were undetectable after 6 months. The study showed that mass screening of family members and contacts by using anti-rK39 ELISA could be a highly reliable tool for early diagnosis and to plan prophylactic treatment of latently infected asymptomatic carriers to eradicate kala-azar.
TL;DR: If applied in a practical clinical setting (on symptomatic patients in whom active VL is suspected and other common infections have been excluded), strip testing of serum for anti-K39 antibody should be both sensitive and specific for diagnosing VL in India.
Abstract: Stored sera from 429 Indian subjects were assayed to extend the analysis of the accuracy of immunochromatographic strip-test detection of anti-K39 antibody in the non-invasive diagnosis of visceral leishmaniasis (VL). All 225 samples from patients with proven Leishmania infection tested positive [estimated sensitivity=100%; 95% confidence interval (CI)=98%-100%]. Sera from 99 of the 100 symptomatic patients with other diseases were non-reactive (estimated specificity=99%; CI=94%-100%). However, samples from 13 of the 104 apparently healthy controls showed positive strip-test results (estimated specificity=88%; CI=79%-93%), yielding an overall specificity of 93% (190/204; CI=88%-96%). If applied in a practical clinical setting (on symptomatic patients in whom active VL is suspected and other common infections have been excluded), strip testing of serum for anti-K39 antibody should be both sensitive and specific for diagnosing VL in India.
TL;DR: Age and ethnic origin of the patients were the most important critical risk factors to account for the distribution of the VL cases that were recorded during the whole epidemic and host genetic factors played an important role in shaping the outbreak in this village.
TL;DR: The findings suggest that A2 protein is a potential tool for the diagnosis of VL in the New World, and will be particularly useful for diagnosis of dogs.
TL;DR: Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar, according to posttreatment apparent cure and definite cure rates.
Abstract: In this randomized, double-blind, dose-ranging, multicenter trial, 84 patients with visceral leishmaniasis refractory to antimony therapy were administered liposomal amphotericin B (AmBisome) at cumulative doses of 3.75, 7.5, and 15.0 mg/kg for 5 consecutive days. Posttreatment apparent cure and definite cure were assessed at 2 weeks and 6 months after the end of therapy, respectively. Mild to moderate infusion-related fever and rigors were seen in 29 and 44% of patients, respectively. One patient each in the 3.75- and 7.5-mg groups had detectable parasites on splenic smear at posttreatment evaluation. At 6 months' follow-up, however, 2, 1, and 1 patients relapsed in the 3.75-, 7.5-, and 15.0-mg groups, resulting in definite cure rates of 89, 93, and 97%, respectively. There was no significant difference in the cure rates of the 3 groups. Low-dose liposomal amphotericin B given for 5 days can cure most patients with Indian kala-azar.
TL;DR: The results suggest that the detected antigen is highly specific and diagnostic for VL, and is the target antigen in the previously described latex agglutination test ('KATEX').
TL;DR: Spatial analytical techniques can identify high-risk areas for targeting control interventions in Brazilian cities, and a locally weighted (LOESS) regression model demonstrated large-scale variation, with high incidence rates in peripheral neighborhoods that bordered forest land and pastures.
Abstract: Background. The pattern of spread of visceral leishmaniasis in Brazilian cities is poorly understood.Methods. We used geographic information systems and spatial statistics to evaluate the distribution of 1061 cases of visceral leishmaniasis in Teresina, Brazil, in 1993 through 1996.Results. A locall
TL;DR: No firm conclusion as to the difference in incidence of VL between the two villages could be reached but differences in exposure to VL and cutaneous leishmaniasis (CL) as well as other factors such as ethnic background and differences in nutritional status may play a role.
Abstract: We conducted a longitudinal study in an endemic area for visceral leishmaniasis (VL) in eastern Sudan to compare the epidemiology and clinical spectrum of Leishmania donovani infection in two populations differing in ethnic background and duration of residence in the area. The study took place in two villages from April 1994 to April 1996. In Um-Salala village, which is inhabited by members of the Masaleet tribe, half of the villagers had previous exposure to cutaneous leishmaniasis (Leishmaria major) before moving there. The population of the second village, Mushrau Koka, belong to the Hausa tribe and most were born there. The incidence of VL was 20.4/1000 person-years in 1994/1995 and increased sharply to 38.3/1000 person-years in 1995/1996 in Um-Salala. A rise in the incidence of VL was also observed in Mushrau Koka but with a lower incidence, 3.3/1000 person-years to 4.6/1000 person-years. The incidence rate of confirmed VL reflects only a limited part of the total infection rate which includes various forms of subclinical infection. The ratio of clinical to subclinical infection in Um-Salala was 1.2 : 1 in 1994/1995 compared with 2.6 : 1 in 1995/1996. This ratio was 1 : 11 in 1994/1995 and 1 : 2.5 in 1995/1996 in Mushrau Koka. In both villages the mean age of subclinical cases was higher, but in Mushrau Koka the mean age of subclinical cases also was higher than that of subclinical cases in Um-Salala. The leishmanin skin test (LST) was positive in 56% of individuals in Um-Salala and in 33% in Mushrau Koka. VL only occurred in leishmanin-negative individuals. Post kala-azar dermal leishmaniasis (PKDL) followed in 58% of confirmed VL patients in Um-Salala; the low incidence of VL for Mushrau Koka did not permit to estimate a PKDL rate. The clinical manifestations resulting from exposure to L. donovani range from subclinical infection to VL and PKDL. No firm conclusion as to the difference in incidence of VL between the two villages could be reached but differences in exposure to VL and cutaneous leishmaniasis (CL) as well as other factors such as ethnic background and differences in nutritional status may play a role.
TL;DR: It is postulate that the decline in childhood visceral leishmaniasis in southern Europe in the second half of the 20th century is related to social changes, which gave rise to a less frequent exposure at a young age as well as a lowered susceptibility to disease through nutritional and immune improvements.
Abstract: A study of leishmanin skin test reactors was carried out in 1997 and 1998 in an endemic region in southeast Spain, to estimate the magnitude of and the factors related to subclinical Leishmania infantum infection. In the main focus of leishmaniasis in the region, 11·5% of the children and 52·8% of the adults reacted to the skin test. Among the adults, the response was significantly greater for males and for those who had resided in the area for ≥ 15 years. In the whole region, 3·7% 14-year-old students reacted to the skin test, with no gender differences. The main factors related to a positive skin test result were having a parent or sibling recovered from leishmaniasis (relative risk = 14) and living in the rural periphery of the region as opposed to the metropolitan area (relative risk = 4). These results indicate a high frequency of subclinical leishmaniasis in the region. We postulate that the decline in childhood visceral leishmaniasis in southern Europe in the second half of the 20th century is related to social changes, which gave rise to a less frequent exposure at a young age as well as a lowered susceptibility to disease through nutritional and immune improvements.
TL;DR: It is hypothesised that the presence of infected dogs in areas where L shannoni or L youngi occur could initiate new endemic cycles of VL in both South and North America.
TL;DR: The prevalence of infection with Leishmania chagasi in Teresina at the end of the second outbreak is described and the number of people who became infected during the epidemic is estimated to be over 320000.
TL;DR: The DAT is the most suitable test for the sero-diagnosis of VL under field conditions because the reagents used for DAT do not require cold storage, whereas the buffer of the rK39 must be stored at 4oC.
Abstract: The direct agglutination test (DAT) based on a freeze-dried antigen and the rK39 dipstick test were evaluated for the sero-diagnosis of visceral leishmaniasis (VL). The sensitivity and specificity of both tests were determined using sera from confirmed VL patients (n = 21), healthy controls (n = 19) and from patients with other confirmed infectious diseases (n = 42). The DAT had a sensitivity and a specificity of 100%. The rK39 had a sensitivity of 85.7% and a specificity of 82%. Both tests were also used to screen blood samples of confirmed VL patients (n = 15) and serum samples of VL suspects (n = 61). The DAT found all blood samples of confirmed VL patients positive and tested 98.4% of the serum samples of the VL suspects positive. In contrast, rK39 detected in 9/15 blood samples (60%) antibodies against Leishmania chagasi and found 85.3% of the serum samples of the suspected patients positive. Although the rK39 dipstick is more rapid and user friendlier than the DAT, the latter has a superior sensitivity and specificity. Furthermore, the reagents used for DAT do not require cold storage, whereas the buffer of the rK39 must be stored at 4oC. Therefore, the DAT is the most suitable test for the sero-diagnosis of VL under field conditions.
TL;DR: The LMS antigen displayed no cross-reactivity with sera from patients or dogs that had any of the other diseases tested and yielded more reliable results than IFAT.
Abstract: An antigen (LMS) prepared from Leishmania major-like promastigotes was used in an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of human and dog visceral leishmaniasis. The results were compared with those from the indirect immunofluorescent antibody test (IFAT). A total of 1,822 canine sera were tested, including sera from dogs with visceral leishmaniasis, transmissible venereal tumors, ehrlichiosis, rickettsiosis, or Chagas’ disease and sera from healthy dogs. The antigen was also tested with 227 samples of human sera, including sera from patients with visceral, cutaneous, or diffuse cutaneous leishmaniasis and from noninfected individuals, as well as sera from patients with Chagas’ disease, toxoplasmosis, rickettsiosis, hepatitis B, schistosomiasis, ascaridiasis, malaria, rheumatoid factor, leprosy and rheumatoid factor, tuberculosis, or leprosy. All dogs and all human patients had a clinical and/or serological and/or parasitological diagnosis. For detecting antibodies in sera from dogs with leishmaniasis, the antigen showed a sensitivity of 98%, specificity of 95%, and concordance of 93% and when used for detecting antibodies in human sera presented a sensitivity of 92%, specificity of 100%, and concordance of 92%. Comparison between ELISA and IFAT demonstrated that ELISA using the LMS antigen yielded more reliable results than IFAT. The LMS antigen displayed no cross-reactivity with sera from patients or dogs that had any of the other diseases tested. Leishmaniasis comprises a spectrum of diseases widely distributed in tropical and subtropical countries, ranging in severity from self-healing skin lesions to severely mutilating mucocutaneous involvement or visceral infections (kala-azar) caused by the protozoan hemoflagellate Leishmania. The leishmanial diseases, except for cutaneous leishmaniasis, have a lengthy incubation period, an insidious onset, and a chronic course. Kala-azar, or visceral leishmaniasis (VL), is characterized by irregular fever, progressive enlargement of the spleen and liver, leukopenia with marked neutropenia, anemia, emaciation, and discoloration of the skin. Leishmanial infections are accompanied by a dramatic humoral response against some forms of leishmania. A marked increase in immunoglobulin G (IgG) in serum and, to a lesser extent, IgM is the common feature in the majority of kala-azar patient sera (17). The antigens used in immunodiagnosis consist of a repertoire of at least 30 somatic antigens and an unknown number of surface components, and the existence of both heterospecific antigens and specific parasite antigens has been established (23, 27). As a result, to date most immunodiagnostic methods have been hampered by the problem of cross-reactivities of species within a family as well as with phylogenetically
TL;DR: Spontaneous healing is commonly seen in Sudanese patients with PKDL, and persistence of the lesions is frequently associated with non-reactivity in the LST and high levels of anti-leishmanial antibodies.
Abstract: In an exploration of the natural history of post-kala-azar dermal leishmaniasis (PKDL), 134 residents of Sudan who had recently been diagnosed as cases of the disease were investigated. In each case, diagnosis had been based on clinical criteria, the temporal relationship between the rash and the treatment of visceral leishmaniasis (VL), positive results in direct agglutination tests (DAT) and/or leishmanin skin tests (LST), and the exclusion of other skin conditions. The mean (S.D.) age of the subjects was 6.4 (3.0) years. Although PKDL appeared commonest among those aged 4-8 years (P < 0.05), it was most severe in children aged
TL;DR: The utility of this PCR-RFLP analysis in detecting leishmaniasis reinfection in HIV-positive patients is suggested and it is suggested that all 40 patients had infection relapses.
Abstract: In the Mediterranean basin, Leishmania infantum is a major opportunistic parasite in people with acquired immunodeficiency syndrome (AIDS), and up to 9% of the patients with AIDS suffer from newly acquired or reactivated visceral leishmaniasis. Distinguishing between reinfections and relapses in these patients is important because some apparent treatment failures occur in patients with new rather than reactivated infections. Isoenzyme characterization is limited for use in determining relapsed versus newly acquired leishmaniasis in human immunodeficiency virus (HIV)-infected patients because of the variability of L. infantum and the predominance of the MON-1 zymodeme in people coinfected with HIV. A seminested polymerase chain reaction (PCR) was used to amplify L. infantum minicircle kinetoplast DNA, and, after digestion, the restriction fragment-length polymorphism (RFLP) profiles showed that 3 (7.5%) of 40 patients coinfected with L. infantum and HIV had a new infection, whereas isoenzyme characterization indicated that all 40 patients had infection relapses. These results suggest the utility of this PCR-RFLP analysis in detecting leishmaniasis reinfection in HIV-positive patients.
TL;DR: The use of HAART has led to a fall in the incidence of symptomatic VL in HIV-infected patients, and the main risk factor associated with kala-azar emergence in patients infected with HIV is deep immunosuppression.
Abstract: The way in which the extensive use of highly active antiretroviral therapy (HAART) has influenced the incidence of visceral leishmaniasis (VL) among human immunodeficiency type 1 (HIV-1)-infected patients is not yet understood. The present study assessed whether the incidence of symptomatic VL in HIV-infected patients has decreased since the introduction of HAART. Likewise, the role of other potential risk factors for VL was also analyzed. Therefore, 479 HIV-1-infected patients receiving antiretroviral treatment, according to the available drugs at each moment, were prospectively followed from April 1989 to June 2000 in two university hospitals in southern Spain. A bone marrow aspiration was performed when patients showed symptoms suggestive of kala-azar. A diagnosis of VL was made when Leishmania amastigotes were seen in Giemsa-stained samples or promastigotes were cultured in specific media. The median follow-up time was 1,380 [8 to 4,536] days. Twenty-one patients were diagnosed with symptomatic VL. The density of incidence of VL has decreased 64.8% as of January 1997, when HAART began to be used extensively in our area. The use of HAART was the main independent factor associated with VL; this therapy was a protective factor (adjusted hazard ratio [HR], 0.05; 95% confidence interval [CI], 0.02 to 0.15). CDC clinical category C at entry in the cohort (HR, 4.08; 95% CI, 1.46 to 11.35) and CD4+ cell counts below 300 cells/mm3 during the follow-up (HR, 3.96; 95% CI, 1.56 to 10.01) were also independently associated with kala-azar. A VL diagnosis prior to follow-up and low compliance with antiretroviral therapy were not independently associated with symptomatic VL, although statistical significance was almost reached (P = 0.1 and P = 0.08, respectively). In summary, the use of HAART has led to a fall in the incidence of symptomatic VL in HIV-infected patients. The main risk factor associated with kala-azar emergence in patients infected with HIV is deep immunosuppression.
TL;DR: Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates.
Abstract: Leishmaniasis is a protozoan disease whose clinical manifestations depend both on the infecting species of Leishmania and the immune response of the host. Transmission of the disease occurs by the bite of a sandfly infected with Leishmania parasites. Infection may be restricted to the skin in cutaneous leishmaniasis (CL), to the mucous membranes in mucosal leishmaniasis or spread internally in visceral leishmaniasis (VL). In the last 2 decades, leishmaniasis, especially VL, has been recognized as an opportunistic disease in immunocompromised patients, particularly those infected with HIV. Leishmaniasis is characterized by a spectrum of disease phenotypes that correspond to the strength of the host's cell-mediated immune response. Both susceptible and resistant phenotypes exist within human populations. Clinical cutaneous disease ranges from a few spontaneously-healing lesions, to diffuse external or internal disease, to severe mucous membrane involvement. Spontaneously-healing lesions are associated with positive antigen-specific T cell responsiveness, diffuse cutaneous and visceral disease with T cell non-responsiveness, and mucocutaneous disease with T cell hyperresponsiveness. Current research is focused on determining the extent to which this spectrum of host response is genetically determined. In endemic areas, diagnosis is often made on clinical grounds alone including: small number of lesions; on exposed areas; present for a number of months; resistant to all types of attempted treatments; and usually no pain or itching. Multiple diagnostic techniques are available. When evaluating treatment, the natural history of leishmaniasis must be considered. Lesions of CL heal spontaneously over 1 month to 3 years, while lesions of mucocutaneous and VL rarely, if ever, heal without treatment. Consequently, all the latter patients require treatment. Therapy is not always essential in localized CL, although the majority of such patients are treated. Patients with lesions on the face or other cosmetically important areas are treated to reduce the size of the resultant scar. In addition, the species of parasite should be identified so that infection with Leishmania braziliensis and Leishmania panamensis can be treated to reduce the risk of development of mucocutaneous disease. Treating patients with Leishmania and HIV co-infection requires close monitoring for effectiveness of treatment, especially because of the high relapse rates. Proven treatments include: antimonials, pentamidine, amphotericin B, interferon with antimony. Treatments where current clinical experience is too limited include: allopurinol, ketoconazole, itraconazole, immunotherapy, rifampin, dapsone, localized heat, paromomycin ointment and cryotherapy. Investigational treatments include: WR6026, liposomal amphotericin and miltefosine. In addition, vaccines for leishmaniasis are being investigated in clinical trials.