Specific antibody responses as indicators of treatment efficacy for visceral leishmaniasis (original) (raw)
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Pre- and post-treatment antibody levels in visceral leishmaniasis
Transactions of the Royal Society of Tropical Medicine and Hygiene, 1990
Enzyme-linked immunosorbent assay (ELISA) and the direct agglutination test (DAT) were employed to test sera obtained from a visceral leishmaniasis (VL) endemic area, the Aba-Roba focus in southwest Ethiopia. Tlurty sera of untreated VL patients, 37 sera 6-90 months after treatment, 18 sera from endemic controls, 8 sera from non-endemic controls and 23 sera from patients with other diseases (schistosomiasis, tuberculosis, cutaneous leishmaniasis) were tested. Based on ELISA, the percentages negative were found to be 50% up to one year and 89% from 2 to 8 years after treatment. In contrast, these rates based on DAT were 0% in one year and 33% from l-8 years after treatment. The relevance of persisting antibodies in the kinetics and profile of antibody production during treatment is discussed. The use of ELISA in the evaluation of clinical prognosis and patient follow-up is recommended. Se&m from a diffuse cutaneous leishmaniasis patient cross-reacted with the DAT and ELISA for VL.
Novel Antigen Detection Assay to Monitor Therapeutic Efficacy of Visceral Leishmaniasis
The American journal of tropical medicine and hygiene, 2016
Visceral leishmaniasis (VL) diagnosis is routinely performed by invasive splenic, bone marrow, or lymph node biopsies, followed by microscopic identification of the parasites. Conventional serological tests cannot distinguish active disease from asymptomatic VL or from cured infection. Here, we report the initial validation of an enzyme-linked immunosorbent assay (ELISA) assembled to detect the Leishmania infantum/donovani antigens iron superoxide dismutase 1 (Li-isd1), tryparedoxin 1 (Li-trx1), and nuclear transport factor 2 (Li-ntf2) as a tool to monitor therapeutic efficacy of VL. The assembled ELISA detected the antigens in the urine samples from seven VL patients before initiation of therapy. Importantly, the antigens were no longer detected in all patients after completion of the treatment. These preliminary observations point to a promising tool to follow treatment efficacy of VL.
Antileishmanial antibodies in an outbreak of visceral leishmaniasis i
A 3-year longitudinal survey was carried out from 1998 to 2000 in a village in eastem Sudan where a visceral leishmaniasis (VL) outbreak occurred. Leishmania-speciflc antibodies were analysed by enzymelinked immunosorbent assay and immunoblotting. Immunoblot analysis detected antibodies to Leishrnania in 80% of the healthy subjects and half of them harboured high immunoglobulin (Ig) G antibody levels, similar to those of VL patients. These antibodies belonged to the IgG1 and IgG3 subclasses but neither their respective levels nor the immunoblot recognition patterns were predictive of VL. During this epidemic, a large proportion of subjects had a high antileishmanial antibody response, indicating that they were infected by Leishmania though most of them remained healthy during the whole study period. These results obtained in the context of an outbreak contrast with those obtained from studies performed in endemic areas characterized by lower parasite transmission levels. Furthermore, the clinical and serological follow-up of our study subjects showed that VL occurred mainly in subjects who had been serologically positive for 5-24 months rather than resulting from primo infection by the parasite.
Significantly Lower Anti-Leishmania IgG Responses in Sudanese versus Indian Visceral Leishmaniasis
PLoS Neglected Tropical Diseases, 2014
Background: Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response.
PLOS Neglected Tropical Diseases
Background Visceral leishmaniasis is a disease caused by disseminated Leishmania donovani infection which affects almost half a million people annually. Most of the patients are reported from the Indian sub-continent, Eastern Africa and Brazil. In this study, we aimed to determine the levels of antibodies and cytokines in visceral leishmaniasis patients and to examine associations of parasitemia with the clinical states of patients. A prospective study was carried out, enrolling a total of 48 active VL patients who were evaluated before, during different time points and, three months after treatment. Serum cytokine concentrations, antibody levels, parasitemia, laboratory (hematologic and biochemical) measurements, and clinical parameters were assessed. Results Counts of WBC and platelets, and measurements of hemoglobin (Hb) increased during treatment (P ≤ 0.05). Elevated levels of circulating IL-10, IFN-γ, and TGF-β1 were measured before treatment. The observed increase in serum IL-...
Recombinant Leishmania Antigens for Serodiagnosis of Visceral Leishmaniasis
Clinical and Vaccine Immunology, 2005
Serological tests with crude or recombinant Leishmania antigens are important tools for the diagnosis of leishmania infection. However, these tests are not markers of active visceral leishmaniasis (VL), since antibodies to these markers are often observed in individuals with subclinical L. chagasi infection and they do not fall shortly after therapy. In this study, levels of immunoglobulin G (IgG) against three recombinant Leishmania antigens (rH2A, KMP11, and the "Q" protein) were evaluated in sera from individuals with subclinical L. chagasi infection and in patients with VL pre-and posttherapy. The sensitivity of the serological test for diagnosis of VL was 100% with all three antigens. The titers of IgG fell significantly after therapy. While most of the individuals with subclinical L. chagasi infection had antibodies to rH2A and the "Q" protein, only 1 out of 15 individuals had antibodies to KMP11. These data indicate that KMP11 may be used to discriminate L. chagasi infection from active VL and may serve as a marker of response to therapy.
Clinical and Vaccine Immunology, 2005
Several serology-based immunoassays are used to diagnose visceral leishmaniasis (VL), a chronic protozoan parasitic disease caused by the Leishmania donovani complex. These tests are primarily designed to diagnose the most severe clinical form of VL, known as kala-azar. However, leishmanial infection is frequently asymptomatic and may manifest only as a positive serologic response or positive leishmanin skin test. We modified a previously described enzyme-linked immunosorbent assay (ELISA) that detects patient antibodies reactive with the recombinant Leishmania protein K39 (rK39) to confirm suspected kala-azar and to detect asymptomatic infection in a community study in Bangladesh. With the inclusion of a standard curve on each ELISA plate, the rK39 ELISA was more repeatable (kappa coefficient of agreement ؍ 0.970) and more reliable compared to the original method (kappa ؍ 0.587, P < 0.001). The cutoff point for a positive antibody response was chosen based on the 99th percentile of the ELISA distribution for the negative-control sera. However, we found that sera from all patients with active kala-azar yielded values more than twice the magnitude of this cutoff. Using receiver-operator characteristic curves, we determined a second cutoff value predictive of kalaazar. Using these criteria, the sensitivity and specificity of the modified ELISA for kala-azar were 97.0% and 98.9%, respectively, for sera from our study population. We hypothesize that individuals with antibody levels greater than the 99th percentile of the negative controls but less than the cutoff point for kala-azar have asymptomatic leishmanial infections.
New Strategies and Biomarkers for the Control of Visceral Leishmaniasis
Trends in Parasitology, 2019
Effective diagnosis and treatment of visceral leishmaniasis, together with the study of vectors and reservoirs, can lead to a better understanding of the parasite transmission dynamics and the development of more efficient control measures. Recent studies have applied new methodologies and biomarkers, and these have contributed to the early and rapid diagnosis of the disease; assessment of success of pharmacological treatments; efficient monitoring of immunosuppressed individuals; and to population screening for field trials of vaccine efficacy. This opinion article proposes an update to the diagnostic tools for visceral leishmaniasis and their rational and combined use to establish the real prevalence of infection or of exposure to Leishmania in endemic areas. Unveiling the Complexity of Visceral Leishmaniasis Leishmaniasis is a vector-borne infectious disease caused by parasites of the genus Leishmania. Globally distributed, it is poverty-related and is among the deadliest of the neglected tropical diseases (NTDs). Visceral leishmaniasis (VL), caused by Leishmania. donovani and Leishmania infantum, is the most severe clinical form. It affects internal organs and is fatal in 95% of cases if not successfully treated. On some occasions, after an episode of VL caused by L. donovani, the patient may develop a post-kala-azar dermal leishmaniasis (PKDL). So far, little is known about the mechanism by which a patient with VL develops PKDL [1]. The overall incidence of VL has declined in recent years, mainly because of the elimination efforts carried out in South Asia [2]. However, the incidence of VL has increased alarmingly in the Americas, where the recent report by the Pan American Health Organization (PAHO) and the World Health Organization (WHO) indicates that VL is expanding geographically: the number of cases has increased by 26.4%, while the fatality rate and number of deaths have grown progressively since 2014 [3]. In addition, epidemic outbreaks have appeared in Europe, the Indian subcontinent, and Eastern Africa [4-7]. The transmission dynamics (see Glossary) of Leishmania are complex and variable, and are dependent on environmental conditions, the distribution and biology of the vector, the reservoirs involved, and on the health, social, and economic aspects that affect the human host [2]. In the absence of an effective vaccine, the control of VL has been based on the prevention of sand fly bites, the elimination of animal reservoirs (if the VL is zoonotic), and the early detection and effective treatment of human cases [8]. Nevertheless, in regions endemic for VL, most infected individuals remain asymptomatic. Their possible role as 'parasite carriers' with capacity to infect sand flies has been suggested and is under active consideration [9]. Individuals who suffered previous VL infections for which treatment was not fully effective can also remain asymptomatic and subsequently relapse later. Additionally, immunosuppressed patients can remain asymptomatic after VL therapy, because they receive secondary prophylaxis; however, they can still act as reservoirs, as confirmed by xenodiagnoses [10]. This complex scenario for the transmission dynamics of VL makes it even more difficult to establish effective control measures, and highlights the clear need for improved tests that are able to distinguish between all the different conditions (Box 1). Diagnostic tests have to provide an immediate, reliable, confirmatory diagnosis of active VL cases independently of a central laboratory. Improved tests are also necessary to assess treatment success, a fundamental measure for predicting and avoiding relapses. This requires a specific test that goes beyond the clinical recovery of the patient, and the nondetection of the parasite, and confirms cure [11,12].
PloS one, 2015
Diagnostic tests for visceral leishmaniasis that are based on antigens of a single Leishmania strain can have low diagnostic performance in regions where heterologous parasites predominate. The aim of this study was to investigate and compare the performance of five serological tests, based on different Leishmania antigens, in three endemic countries for visceral leishmaniasis. A total number of 231 sera of symptomatic and asymptomatic cases and controls from three endemic regions of visceral leishmaniasis in East Sudan, North India and South France were evaluated by following serological tests: rKLO8- and rK39 ELISA, DAT (ITMA-DAT) and two rapid tests of rK39 (IT LEISH) and rKE16 (Signal-KA). Overall, rKLO8- and rK39 ELISA were most sensitive in immunocompetent patients from all endemic regions (96-100%) and the sensitivity was reduced to 81.8% in HIV co-infected patients from France. Sera of patients from India demonstrated significantly higher antibody responses to rKLO8 and rK39...