Evidence map›Paper›PMID 24732039›Full record

ArticlePloS one2014

Combination of liposomal CpG oligodeoxynucleotide 2006 and miltefosine induces strong cell-mediated immunity during experimental visceral leishmaniasis.

Rahul Shivahare, Preeti Vishwakarma, Naveen Parmar, Pawan Kumar Yadav, Wahajul Haq, Mrigank Srivastava, Suman Gupta, Susanta Kar

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
7.1field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Rahul ShivahareDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Preeti VishwakarmaDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Naveen ParmarDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Pawan Kumar YadavDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Wahajul HaqDivision of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, India.
Mrigank SrivastavaDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Suman GuptaDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Susanta KarDivision of Parasitology, CSIR-Central Drug Research Institute, Lucknow, India.
Central Drug Research Institute · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immuno-modulators in combination with antileishmanial drug miltefosine is a better therapeutic approach for treatment of Visceral Leishmaniasis (VL) as it not only reduces the dose of miltefosine but also shortens the treatment regimen. However, immunological mechanisms behind the perceived benefits of this combination therapy have not been investigated in detail. In the present study, we hypothesized that potential use of drugs that target the host in addition to the parasite might represent an alternative strategy for combination therapy. We investigated immune responses generated in Leishmania donovani infected animals (hamsters and mice) treated with combination of CpG-ODN-2006 and miltefosine at short dose regimen. Infected animals were administered CpG-ODN-2006 (0.4 mg/kg, single dose), as free and liposomal form, either alone or in combination with miltefosine for 5 consecutive days and parasite clearance was evaluated at day 4 and 7 post treatment. Animals that received liposomal CpG-ODN-2006 (lipo-CpG-ODN-2006) and sub-curative miltefosine (5 mg/kg) showed the best inhibition of parasite multiplication (∼97%) which was associated with a biased Th1 immune response in. Moreover, compared to all the other treated groups, we observed increased mRNA expression levels of pro-inflammatory cytokines (IFN-γ, TNF-α and IL-12) and significantly suppressed levels of Th2 cytokines (IL-10 and TGF-β) on day 4 post treatment in animals that underwent combination therapy with lipo-CpG-ODN-2006 and sub-curative miltefosine. Additionally, same therapy also induced heightened iNOS mRNA levels and NO generation, increased IgG2 antibody level and strong T-cell response in these hamsters compared with all the other treated groups. Collectively, our results suggest that combination of lipo-CpG-ODN-2006 and sub-curative miltefosine generates protective T-cell response in an animal model of visceral leishmaniasis which is characterized by strong Th1 biased immune response thereby underlining our hypothesis that combination therapy, at short dose regimen can be used as a novel way of treating visceral leishmaniasis.

Indexed as

Immunity, CellularAnimalsAntiprotozoal AgentsCell ProliferationCricetinaeEnzyme-Linked Immunosorbent AssayImmunoglobulin GImmunologic FactorsLeishmaniasis, VisceralLiposomesMesocricetusMiceMice, Inbred BALB CNitric OxideOligodeoxyribonucleotidesPhosphorylcholineAntiprotozoal AgentsCpG ODN 2006Immunoglobulin GImmunologic FactorsLiposomesmiltefosineNitric OxideOligodeoxyribonucleotidesPhosphorylcholineRNA, Messenger

Identifiers

PMID24732039
PMCPMC3986403
OpenAlexW2125814080

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.