Asymptomatic immune responders to Leishmania among HIV positive patients

Botana, Laura; Ibarra-Meneses, Ana Victoria; Sánchez, C.; Castro, Alicia; Martín, Juan San; Molina, Laura; Ruiz‐Giardín, José Manuel; Carrillo, Eugenia; Moreno, Javier

doi:10.1371/journal.pntd.0007461

Cited by 24 publications

(18 citation statements)

References 32 publications

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“…The SLA extract was prepared from sonicated promastigotes of the stock (MCAN/ES/98/ LLM-722), as described [12]. Heparinized PBMC were separated using a Ficoll-Hypaque gradient (Rafer, Spain), resuspended in complete RPMI supplemented with 10% foetal bovine serum, and cultured (in triplicate) at an initial concentration of 2 x 10 6 cells / ml in 96-well plates with either complete RPMI (negative control) or SLA (10 μg / ml).…”

Section: Cpa-sla Testingmentioning

confidence: 99%

Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context

Molina¹,

Jiménez²,

García‐Martínez³

et al. 2020

PLoS Negl Trop Dis

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Background In the Mediterranean basin, Leishmania infantum is the causative agent of visceral leishmaniasis (VL), a zoonosis in which the dog is the primary domestic reservoir, although wildlife may have a leading role in the sylvatic cycle of the disease in some areas. Infections without disease are very frequent. There is limited information regarding the role that VL patients and asymptomatic infected individuals could be playing in the transmission of L. infantum. Xenodiagnosis of leishmaniasis has been used in this descriptive study to explore the role of symptomatic and asymptomatic infected individuals as reservoirs in a recent focus of leishmaniasis in southwestern Madrid, Spain. Methodology and main findings Asymptomatic blood donors (n = 24), immunocompetent patients who were untreated (n = 12) or treated (n = 11) for visceral leishmaniasis (VL), and immunocompromised patients with VL (n = 3) were enrolled in the study. Their infectivity to Phlebotomus perniciosus was studied by indirect xenodiagnosis on peripheral blood samples. Quantitative polymerase chain reaction of blood samples from immunocompetent patients untreated for VL and immunocompromised untreated, treated and under secondary prophylaxis for VL was performed. Antibodies against Leishmania were studied by indirect fluorescent antibody and rK39-immunochromatographic tests. A lymphoproliferative assay with a soluble Leishmania antigen was used to screen for leishmaniasis infection in the healthy population. Sixty-two xenodiagnostic tests were carried out and 5,080 sand flies were dissected. Positive xenodiagnosis was recorded in four patients, with different sand fly infection rates: 1 immunosuppressed HIV / L. infantum coinfected asymptomatic patient, 1 immunosuppressed patient PLOS NEGLECTED TROPICAL DISEASES

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Section: Cpa-sla Testingmentioning

confidence: 99%

Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context

Molina¹,

Jiménez²,

García‐Martínez³

et al. 2020

PLoS Negl Trop Dis

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“…On the other hand, asymptomatic Leishmania infection has been detected by PCR and LST in HIV+ patients without any history of cutaneous or visceral leishmaniasis [59]. Cellular tests have also been useful for detecting asymptomatic subjects in a cohort of solid organ transplant recipients [60] and of HIV+ patients with no previous leishmaniasis [61].…”

Section: Leishmaniasismentioning

confidence: 99%

Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases

et al. 2020

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Progress has been made in the control or elimination of tropical diseases, with a significant reduction of incidence. However, there is a risk of re-emergence if the factors fueling transmission are not dealt with. Although it is essential to understand these underlying factors for each disease, asymptomatic carriers are a common element that may promote resurgence; their impact in terms of proportion in the population and role in transmission needs to be determined. In this paper, we review the current evidence on whether or not to treat asymptomatic carriers given the relevance of their role in the transmission of a specific disease, the efficacy and toxicity of existing drugs, the Public Health interest, and the benefit at an individual level, for example, in Chagas disease, to prevent irreversible organ damage. In the absence of other control tools such as vaccines, there is a need for safer drugs with good risk/benefit profiles in order to change the paradigm so that it addresses the complete infectious process beyond manifest disease to include treatment of non-symptomatic infected persons.

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“…Leishmania Antigen (SLA). L. donovani and L. infantum antigens were prepared from promastigote cultures in the stationary phase (S-698 strain MHOM/ET/67/HU3 and JPC strain MCAN/ES/98/LLM-722, respectively) as previously described [28,29]. The parasites were first washed with 1X phosphate-buffered saline (PBS) and centrifuged at 1000 g for 20 min at 4°C.…”

Section: Preparation Of Solublementioning

confidence: 99%

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

Aleka

Ibarra-Meneses

Workineh

et al. 2020

Journal of Immunology Research

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Visceral leishmaniasis (VL) is a lethal disease if left untreated. Current treatments produce variable rates of treatment failure and toxicity without sterile cure, rendering treatment efficacy monitoring essential. To avoid repeated invasive tissue aspirates as well as empirical treatment, there is a need for new tools that allow a less-invasive and early assessment of treatment efficacy in the field. Cross-sectional studies have suggested levels of cytokines/chemokines after whole blood stimulation as good markers of cure, but longitudinal studies are lacking. In this study, we followed 13 active VL cases in an endemic area in Ethiopia by measuring the production of IFN-γ, TNF-α, IP-10, IL-2, IL-10, MCP-1, and MIG before, during, and at the end of treatment. After 24 hours of stimulation of whole blood with soluble Leishmania antigen, we observed an early, robust, and incremental increase of IFN-γ, TNF-α, and IP-10 levels in all patients during treatment. Moreover, based on the IFN-γ levels that showed an average 13-fold increase from the time of diagnosis until the end of treatment, we could almost perfectly discriminate active from cured status. Similar concentrations and patterns were found in stimulation assays with the two main Leishmania species. The levels of IFN-γ, IP-10, or TNF-α also seemed to be inversely associated with the parasite load at baseline. Despite a 1/10 drop in concentrations, similar patterns were observed in IFN-γ and IP-10 levels when dried plasma spots were stored at 4°C for an average of 225 days. All the above evidence suggests a detectable restoration of cell-mediated immunity in VL and its association with parasite clearance. With a potential application in rural settings by means of dried plasma spots, we recommend to further explore the early diagnostic value of such assays for treatment efficacy monitoring in large cohort studies including treatment failure cases.

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Asymptomatic immune responders to Leishmania among HIV positive patients

Cited by 24 publications

References 32 publications

Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context

Role of asymptomatic and symptomatic humans as reservoirs of visceral leishmaniasis in a Mediterranean context

Implications of asymptomatic infection for the natural history of selected parasitic tropical diseases

Whole Blood Stimulation Assay as a Treatment Outcome Monitoring Tool for VL Patients in Ethiopia: A Pilot Evaluation

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